Dental Physiology 121
Dr. Donald B. Thomason, Lecture Outlines and Guides
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2005 Lecture Schedule:

Date
PDF files
Online graphics/quizzes
Jan 3 Mon Fluid compartments, cell membranes, diffusion
Mediated transport, osmosis
Jan 4 Tue Cell potentials
Graded potentials, action potentials
Jan 10 Mon Action potential propagation, nerve conduction
Synaptic transmission, neuromuscular transmission
Jan 11 Tue Neurotransmitters, neuromodulators, and the autonomic nervous system
Skeletal muscle contraction mechanism and mechanics
Jan 13 Thu Skeletal muscle mechanics, smooth muscle contraction
Muscle contraction, reflexes
Jan 20 Thu Conference #1 Ions and their movement

Some quizzes and answers as a text file.

Small Group Conference study question answers.

Office hours 3-5 P.M. Wednesdays, or by appointment.

 

Fluid compartments, Cell membranes, Diffusion

Objectives:
The student should be able to:
1. List the major fluid compartments and their relative size.
2. List the major chemical components of cell membranes.
3. State the major functions of a cell membrane.
4. List the types of membrane junctions that can be formed by cells.
5. Indicate the direction of passive net flux of a substance of known concentration.
6. Explain the dependence of flux magnitude on concentration difference, temperature, molecule mass, and surface area.
7. Identify the factors in Fick’s law.
8. Define diffusion coefficient.

Outline:

I. Fluid compartments

A. Total body water (TBW). Approximately 60% of the total body weight is water.  (slide)

B. Intracellular fluid (ICF). Approximately two-thirds of the TBW. (slide)

C. Extracellular fluid (ECF). Approximately one-third of the TBW.

D. The ionic composition of ICF and ECF are different.

E. The ECF is compartmentalized. (slide)

1. Plasma. Approximately 20% of the ECF circulates as the plasma component of blood.

2. Interstitial. Approximately 80% of ECF surrounds the cells that are not in the vascular system.

3. Protein concentration is higher in plasma than in the interstitial fluid.

F. The ICF is compartmentalized within the cell:

1. cytosolic fluid, the fluid within the cells that surrounds the organelles (e.g., nuclei, mitochondria);

2. organellar fluid, the fluid within the organelles.

G. Movement of substances and water between compartments is an important process. (quiz)

II. Cell membranes

A. A cell’s plasma membrane is a selective barrier to water and ion movement.

1. It separates the cytoplasm (cytosolic and organellar fluid) from the extracellular fluid.

2. It allows tightly coupled cells to act as a barrier between fluid compartments (e.g., the cells that separate the plasma from the insterstitial fluid).

B. Composition

1. Lipid bilayer (plasmalemma) a. consists of amphipathic phospholipids molecules (slide)

b. arranged in a bilayer with hydrophilic head groups pointed toward the aqueous phase (slide)

c. hydrophobic fatty acid side-chains are in the interior of the bilayer

d. the membrane is fluid

e. cholesterol and unsaturated fatty acid side-chains help maintain fluidity of the bilayer (slide)

2. Proteins

a. integral (slide) i. transmembrane

ii. single-sided

b. peripheral

c. glycoproteins — extracellular carbohydrate attached to membrane proteins

3. Other substances

a. cholesterol

b. hydrophobic substances

i. hormones

ii. fatty acids

iii. drugs

(quiz)
C. The fluid mosaic model of membrane structure

D. Membrane junctions

1. Junctional proteins (e.g., integrins) are transmembrane proteins that link cells to one another and to the extracellular matrix. (slide)  

2. Desmosomes provide a mechanical linkage between cells. (slide)

 

3. Tight junctions and their proteins provide an impermeant barrier by closely linking adjacent cells. This produces a "sidedness" to the cells so that substances moving from one side to the other must cross through the cells. (slide)
4. Gap junction proteins allow cell-to-cell communication. (slide)

(quiz)
III. Diffusion in free solution

A. Diffusion direction and magnitude

1. Diffusion is a random process (slide) a. random thermal motion

b. probability of directional movement depends upon concentration
 

2. If fluid compartments are separated by a permeable membrane, the difference in probability of movement from one compartment to another is the net flux. (slide)

 

3. In the absence of transport mechanisms (discussed later), net flux is always from high concentration to low concentration (passive net flux).

 

4. The magnitude of flux of a molecule across a permeable membrane depends upon:

 
a. concentration difference of the molecule on both sides of the membrane;

b. temperature of the solutions;

c. size of the molecule;

d. area of the membrane.

B. Diffusion as a function of time and distance (Fick’s equation)

1. Net flux from diffusion in free solution depends upon the concentration gradient of the substance: Dc/Dx.  

2. The larger the concentration gradient, the larger the net flux.

 

3. The constant of proportionality that relates flux (J) to the concentration gradient is the Diffusion coefficient (D). Fick’s equation is:

J = -D· (Dc/Dx)

4. The units of D are cm2/sec.

 

5. Diffusion over short distances is fast, but over long distances diffusion is very slow.

IV. Diffusion across cell membranes

A. Adaptation of Fick’s equation

1. Net flux across a cell membrane depends upon the concentration difference of the substance: (Co - Ci), where Co is the concentration outside the cell, and Ci is the concentration inside the cell.  

2. The net flux depends on the surface area of the cell membrane, A

 

3. The constant of proportionality that relates flux (J) to the concentration difference and the membrane area is the permeability coefficient (kp). Flux from outside to inside is:

J = kp·A· (Co-Ci)

B. The diffusion of a hydrophilic substance (e.g., an ion) across a hydrophobic membrane is very slow because the permeability coefficient is usually very small.

C. Hydrophobic substances and gases have a much higher permeability coefficient.

D. Integral membrane proteins can selectively increase the permeability coefficient for particular substances, such as ions. (slide)

1. These "channels" (pores) and transporters (carriers) recognize specific substances, and thus are selective.

2. Channels provide a semi-aqueous path for free diffusion.

3. Transporters provide a protein-mediated transport mechanism that may couple the transport of one substance against its gradient to the flux of another substance "down" its flux gradient (discussed later).

4. They can be regulated to increase or decrease permeability

 
a. transporters may be modified to change the rate of transport

b. channels can be "gated" on and off by:

i. electrical activity

ii. ligand binding

iii. modification by enzymes

iv. mechanical deformation.

E. Separation of charge across a membrane will also affect diffusion of ions across the membrane.

1. A net charge will attract or repel an opposite or like charged ion, respectively. This will affect the flux of the ion.

2. The electrical force acting on an ion may be opposite in direction from the chemical force driving diffusion (chemical gradient). Thus, an ion experiences an "electrochemical gradient" that influences flux.

 

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Mediated transport, Osmosis

Objectives:
The student should be able to:
1. State the molecular mechanism of protein-mediated transport across a cell membrane.
2. List the properties of protein-mediated transport.
3. List the determinants of flux magnitude.
4. List the types of protein-mediated transport and the driving force for each.
5. Indicate the direction of water movement across a cell membrane for a given extracellular fluid tonicity.
6. Explain the difference between tonicity and osmolarity.

Outline:

I. Mechanisms and characteristics of mediated transport

A. Protein-mediated transport relies on integral membrane proteins to "carry" a substance across the membrane. (slide) (animation)

1. Molecular mechanism is a conformational change in the protein (change in protein folding) such that the bound substance has access to both sides of the membrane.

2. The substance must diffuse to and from the transporter.

3. Transport takes place in the direction of the most energetically favorable gradient unless energy is expended to "push" a molecule "up" its concentration gradient.

B. Properties of protein-mediated transport

1. Faster than diffusion through the membrane, i.e., lowers the energy barrier of the hydrophobic bilayer. Channels > transporters.

2. Specific for a particular chemical species or class of molecules

3. Saturable because of a finite number of transporters in a cell membrane.

4. Competitively inhibited by similar substances

5. Inhibitable by drugs and like substances to decrease permeability coefficient.

C. Determinants of the flux magnitude by protein-mediated transport mechanisms

1. Number of transporters.

2. Saturation of the transporters.

3. Rate of conformational change of the transporter.

II. Types of protein-mediated transport mechanisms

A. Facilitated

1. Independent of membrane permeability.

2. Facilitated by electrochemical gradients.

3. Maintained by "disposal" (often metabolic) of the transported substance.
 

(quiz)
B. Active, primary. (slide)

1. Depends directly on the expenditure of energy by the transporter.

2. Can transport substances "up" their concentration gradient.
 

C. Active, secondary (slide)

1. Depends indirectly on the expenditure of energy for the primary active transport of an ion

2. Couples the transport of the ion moving "down" its electrochemical gradient to provide the energy required to move another substance "up" its electrochemical gradient.

3. Types of coupled transport:

a. symport

b. antiport

(quiz)
III. Osmosis

A. The concentration of water and solutes in solution.

1. Osmolarity (slide).

a. function of the number of particles dissolved in solution.

b. the particles take up space, decreasing the concentration of water.

c. water will move down its concentration gradient.

d. specific channels/transporters for water exist in cell membranes

2. Penetrating and non-penetrating solutes.

a. penetrating solutes are permeable to the cell membrane. i. if they equilibrate across the membrane, they will affect water concentration to the same extent on both sides of the membrane.

ii. example is urea.

b. non-penetrating solutes cannot cross the cell membrane.

i. they will affect water concentration only on the side of the membrane where they are "trapped."

ii. example is albumin

B. Tonicity versus Osmolarity (slide)

1. Tonicity is the concentration of impermeant, osmotically active substances in solution.

a. an isotonic solution is roughly 300 mOsm/l dissolved substances.

b. e.g., a living cell has approximately 300 mOsm/l total K+, protein, and Cl- inside, so a bathing solution of 150 mM/l NaCl (300 mOsm/l) is isotonic (all of these substances are relatively impermeant to a living cell).

2. Osmolarity is the concentration of both permeant and impermeant substance in solution.

a. permeant substances will cross the membrane fairly quickly compared to water.

b. therefore, the substance will equilibrate before much water movement (down its gradient) has taken place.

3. A solution need not have its tonicity = osmolarity, e.g.

a. a 7% sucrose solution is isotonic and isoosmotic;

b. a 10% ethanol solution is hyperosmotic;

c. a 7% sucrose, 10% ethanol solution is isotonic and hyperosmotic.

(quiz)
C. The movement of water across a semipermeable membrane.

1. Diffusion and transport.

2. Tonicity and cell volume.

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Cell Potentials

Objectives:
The student should be able to:
1. Write Ohm’s law, define the factors, and state an analogy for each factor.
2. Calculate the equilibrium potential for an ion at 37°C.
3. State the fundamental reason for the passive segregation of ions across a cell membrane.
4. State the role of active transport in the segregation of ions across a cell membrane.
5. List the relative intracellular and extracellular concentrations of the major ions.
6. State why the resting membrane potential is often near the potassium equilibrium potential.
7. State the relative resting permeability of a membrane to sodium relative to potassium.

Outline:

I. Basic principles

A. Ohm’s law describes the relationship between the flow of electrons (ions), the force driving the flow, and the resistance the flow encounters.

B. Mathematically, Ohm’s law is stated as: (slide)

I=E/R, or E=I x R, where

1. E is potential, the driving force or "pressure" on electrons to move;

2. R is resistance, the opposition to flow that the electrons encounter;

3. I is current, the number of electrons that are moving for a given driving force (E) and resistance to flow (R).

II. The resting membrane potential

A. Segregation of ions across a membrane generates electrical potential

1. Nernst equation - chemical potential, electrical potential, and equilibrium
  a. The chemical energy (or work) of moving an ion Xz from one concentration inside a cell to another concentration outside the cell is

b. The electrical energy (or work) of moving an ion Xz through an electrical potential across the membrane (E, measured outside relative to inside) is

c. The ion will come to equilibrium when the electrical work is equal to the chemical work:

(quiz)

d. This is the ion’s equilibrium potential, EX .

e. In practice, the equation can be written, for body temperature of 37°C, as

(quiz)

2. Passive segregation (Gibbs-Donnan equilibrium) (slide)
 

a. The membrane is selectively permeable to certain substances through the transport mechanisms discussed previously and slow leaks.

b. Intracellular protein is not permeable, so it is trapped inside the cell.

c. The net charge on intracellular protein is negative.

d. This negative charge would like to be balanced by a positive charge (usually K+), so the protein "holds" potassium ions inside the cell.

e. Considering the simple case of protein, K+, and Cl-, what happens to ion distribution?

i. an equilibrium can develop, so

ii. but, by definition, at equilibrium EK=ECl , so

iii. so, protein holding K+ inside the cell will force chloride to be at a higher concentration outside the cell than inside

iv. therefore, protein caused the passive segregation of potassium and chloride ions. As we shall see, if the permeability of the membrane is greater for potassium than chloride (which would not affect the equilibrium), an electrical potential develops across the membrane.

3. Active segregation
 

a. Active transport of ions can be electrogenic by
  i. producing concentration gradients, and/or

ii. moving net charge
 

b. Examples
 

i. sodium-potassium ATPase - 3 sodium ions pumped out for every 2 potassium ions pumped in. (slide)

ii. calcium pump - plasmalemma and organelles (slide)
 

4. Together, active and passive segregation generate ion gradients across a membrane. (slide)

5. In many cells, the resting membrane potential (voltage) is very near the potassium equilibrium potential. We shall see why in the next section. (slide) (animation)

B. Membrane permeability of ions determines the resting membrane potential

1. Given a membrane permeability (P) for each monovalent ion, a generalization of the Nernst equation is the constant field equation:

2. Rather than measure each ion’s permeability, the permeability is expressed relative to the membrane permeability to potassium:

Often, under resting conditions, PK >> PNa , PCl , so membrane potential is close to the equilibrium potential for potassium. (quiz)

3. How many ions must move to significantly change membrane potential? Very few, not enough to significantly change bulk ion concentration.

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Graded Potentials, Action Potentials

Objectives:
The student should be able to:
1. Describe a graded potential.
2. State how stimulus polarity and magnitude affect a graded potential.
3. Define spatial and temporal summation of graded potentials.
4. List the sequence of membrane permeability changes responsible for an action potential.
5. Define absolute and relative refractory periods.
6. Describe how some anesthetics can block nerve activity.

Outline:

I. Graded potentials

A. Opposite charges attract one another, and therefore will dissipate to electroneutrality.

B. A local perturbation in membrane potential: (slide)

1. affects the membrane potential at some distance from the site of the perturbation;

2. decrements over time and distance;

3. produces local currents because of the charge movement.

C. Features of a graded potential:

1. change from the resting membrane potential can be either more positive (depolarization) or negative (hyperpolarization); (slide)

2. depends upon the initial stimulus magnitude; (slide)

3. decrements over distance and time;

4. summates with other stimuli in time and space (both positive and negative). (slide)

(quiz)
(quiz)
D. If a depolarizing graded potential is sufficiently large, it will produce an action potential (below).

II. Action potentials

A. There is a threshold potential for stimulation of an action potential (slide)

1. voltage-gated sodium channels are normally closed at resting membrane potentials (low sodium permeability);

2. near the threshold potential some channels begin to open, allowing sodium to flow in and further depolarize the membrane;

3. more sodium channels open, further depolarizing the membrane and opening most or all of the sodium channels (regeneration);

4. the membrane potential will approach the sodium equilibrium potential because of the high membrane permeability to sodium relative to potassium.

B. Changes in membrane permeability are responsible for the shape of the action potential. (slide) (animation)

1. sodium channels open in response to a suprathreshold stimulus, causing the membrane potential to "spike" near the sodium equilibrium potential because the potassium permeability is low relative to the sodium permeability;

2. sodium channels also exhibit a rapid voltage-dependent inactivation that occurs at potentials more positive than the resting membrane potential;

3. sodium channel inactivation begins to decrease the sodium permeability;

4. at the same time sodium channels are inactivating the potassium channels begin a voltage-gated activation, increasing the potassium permeability;

5. the increased potassium permeability combined with the decreased sodium permeability returns the membrane potential to rest or even hyperpolarized potentials;

6. at the resting potential potassium channels close once again and the spontaneous inactivation of the sodium channels "resets."

(quiz)
C. The membrane becomes refractory to another action potential during and for a time following an action potential. (slide)

1. sodium channel inactivation is "reset" only at membrane potentials at or hyperpolarized below the resting membrane potential;

2. it takes a period of time several times longer than the action potential for the sodium channels to reset;

3. during and immediately following the action potential the membrane is in a absolute refractory period because no amount of stimulus can open the inactivated sodium channels;

4. as time progresses more and more sodium channels are reset, so that some may be opened;

5. initially a greater than threshold stimulus is required to generate an action potential because not all the sodium channels have reset (relative refractory period);

6. as more time elapses the stimulus intensity required to produce an action potential returns to the normal threshold level.

D. In some cell types other ions may participate in the action potential, e.g., calcium moving similarly to sodium from a high concentration outside the cell to a low concentration inside through a regenerative calcium channel.

E. The initial stimulus for the threshold depolarization may:

1. arise from voltage-gated changes in membrane permeability;

2. arise from ligand-gated changes in membrane permeability (e.g., increased sodium influx);

3. be inhibited by hyperpolarizing changes in membrane permeability.

F. Many anesthetics block the opening of the sodium channel or the flux of sodium through the channel, preventing a threshold stimulus from initiating an action potential.
(quiz)
 

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Action Potential Propagation, Nerve Conduction

Objectives:
The student should be able to:
1. Define the necessary condition for an action potential to propagate along a membrane.
2. List two examples demonstrating the importance of refractoriness to organized action potential propagation.
3. State the role of pacemaker potentials for action potential generation.
4. State the effect of nerve fiber size on the rate of action potential propagation.
5. State the effect of nerve fiber myelination on the rate of action potential propagation.
6. Define saltatory conduction.

Outline:
I. Action potential propagation

A. Local circuit currents from a local depolarization of a membrane cause adjacent membrane to depolarize.

1. the depolarization, as discussed for graded potentials, decrements over time and distance. (slide)

2. suprathreshold potentials, such as the peak of an action potential, will bring adjacent membrane above threshold for action potentials in that area of membrane. (slide)

B. Refractoriness of the membrane following an action potential "directs" the action potential in the direction of membranes that are not refractory. (slide)

1. prevents antidromic conduction in nerve fibers.

2. prevents "circus rhythms" from developing in the heart (fibrillation).

(quiz)
C. Initiation of an action potential in electrically excitable cells.

1. Stimulus-induced changes in membrane permeability. (slide)
a. sodium

b. calcium

c. potassium

2. Spontaneous pacemaker potentials are usually a result of rhythmic changes in potassium permeability. (slide)


II Nerve conduction

A. Effect of fiber diameter

1. larger diameter fibers have a larger "space constant" determined by the membrane internal fiber resistance to current flow (from local circuit currents). (slide)

2. locations further from the action potential will be brought to threshold, thus moving the action potential along more rapidly.

(slide)

B. Effect of myelin.

1. dramatically increases the space constant by increasing membrane resistance in myelinated areas. (slide)
(quiz)

2. rather than a linear conduction, the action potential appears to rapidly "jump" from one Node of Ranvier to another (saltatory conduction).(animation)

(quiz)
(quiz)
 

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Synaptic Transmission, Neuromuscular Transmission

Objectives:
The student should be able to:
1. List the two types of post-synaptic potentials and an ionic basis for each.
2. State the fundamental role of the post-synaptic membrane to the principal of convergence.
3. List the two broad categories of synaptic transmission.
4. List or draw the sequence of events required for chemical synaptic transmission.
5. State the quantal theory of neurotransmitter release.
6. Define neuromodulation.

Outline:
I. Neuronal connectivity

A. Forms of information transmitted
 

1. excitatory synapses produce an excitatory post-synaptic potentials (EPSPs) at the "end-plate" (as synapses are sometimes called). Possible causes: (slide)
a. increased sodium permeability;

b. decreased potassium permeability;

c. increased calcium permeability.

2. inhibitory synapses produce an inhibitory post-synaptic potentials (IPSPs). Possible causes: (slide)

a. increased potassium permeability;

b. decreased sodium permeability (in some cells). (quiz)

(quiz)
B. Dissemination of information (slide)

1. convergence. Many pre-synaptic excitatory and inhibitory neurons may converge on a single post-synaptic neuron. This neuron will integrate EPSPs and IPSPs.

2. divergence. A single presynaptic neuron may make connections with many post-synaptic neurons.


II. Types of synaptic transmission

A. Electrical. Electrical conduction through gap junctions. Rare in mammals.

B. Chemical

1. requirements: (slide)
a. synaptic cleft to bring neurotransmitter release site close to the neurotransmitter receptors;

b. pre-synaptic release of neurotransmitter in response to a signal (usually an action potential); requires:

i. calcium entry into the pre-synaptic nerve ending;

ii. calcium-dependent fusion of neurotransmitter containing vesicles with the cell membrane.

c. diffusion of the neurotransmitter across the synaptic cleft;

d. post-synaptic binding of the neurotransmitter to its receptor (often a channel);

e. a chemical change in the post-synaptic cell due to receptor action (often a change in permeability to an ion);

f. removal of the neurotransmitter from the synaptic cleft to halt the transmission.

(quiz)
(quiz)

2. quantal theory of synaptic transmission (slide)
a. in a "resting" post-synaptic membrane miniature end-plate potentials are observed;

b. they are very regular in their magnitude;

c. they exhibit spatial and temporal summation;

d. occur from the random, spontaneous fusion of neurotransmitter containing vesicles with the presynaptic neuron membrane, causing release of "quanta" of neurotransmitter.


III. Post-synaptic response

A. Excitatory

B. Inhibitory

C. Summation

1. temporal

2. spatial

D. Neuromodulation
 

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Neurotransmitters, Neuromodulators, and the Autonomic Nervous System

Objectives:
The student should be able to:
1. List three neurotransmitters and their mode of action.
2. State the two branches of the efferent peripheral nervous system.
3. State the anatomical distinction between the somatic and autonomic nervous system.
4. List the target organs of the autonomic nervous system.
5. State the neurotransmitters, their receptors, and their anatomical location of the parasympathetic nervous system.
6. State the neurotransmitters, their receptors, and their anatomical location of the sympathetic nervous system.
7. Define autonomic balance.
 

Outline:
I. Neurotransmitters and neuromodulators

A. Classification

1. Anything can act as a neurotransmitter or neuromodulator if:
a. it is release from a nerve;

b. it binds to a target and conveys a signal or modifies a signal;

c. the signal decays or is removed.

2. Drugs can act as neurotransmitters or neuromodulators if they:

a. are structurally similar to an endogenous substance so that they act as an
i. agonist

ii. antagonist

b. block

i. release of an endogenous substance;

ii. action of an endogenous substance;

iii. disposal of an endogenous substance.

c. facilitate

i. release of an endogenous substance;

ii. action of an endogenous substance;

iii. disposal of an endogenous substance.

B. The better known neurotransmitters and neuromodulators are:

1. Acetylcholine
a. cholinergic neurons found through the body

b. binds to an acetylcholine receptor

i. nicotinic - cation channel

ii. muscarinic - G protein coupled receptors

c. hydrolyzed by acetylcholinesterase

2. Biogenic amines

a. catecholamines (epinephrine, norepinephrine, dopamine)
i. adrenergic neurons found throughout the body

ii. adrenergic receptors

iii. taken up at nerve terminal and also disposed of by monoamine oxidase

b. 5-hydroxytryptamine (serotonin)

i. neurons are primarily CNS

ii. probably neuromodulatory

iii. taken up at nerve terminal and also disposed of by monoamine oxidase

c. histamine

i. neurons found throughout body

ii. both afferent and efferent nerves

a. vasodilatory
b. pain and itch sensation

3. Amino acids

a. excitatory (increase sodium and cation permeability)
i. glutamate

ii. aspartate

iii. taken up at nerve terminal ?

b. inhibitory (increase chloride permeability)

i. g-aminobutyric acid (GABA)

ii. glycine

iii. taken up at nerve terminal.

4. Neuropeptides

a. often classified as neuroendocrine

b. endogenous opioids are notable members of this class

5. Metabolic products

a. usually neuromodulators, often as endocrine substances

b. include

i. nitric oxide

ii. ATP

iii. adenosine

(quiz)

II. Peripheral nervous system

A. Afferent - sensory nerves that lead toward the CNS

B. Efferent (slide)

1. Somatic
a. primarily skeletal muscle innervation

b. single neuron originating in the CNS

2. Autonomic

a. two neurons
i. preganglionic originates in the CNS

ii. postganglionic target effector organ or cells

a. smooth muscle (eye, gut, vascular, urinary)
b. heart
c. glands
d. GI neurons

b. can be either excitatory or inhibitory

III. Autonomic nervous system

A. Parasympathetic (slide)

1. both pre- and postganglionic neurons are cholinergic

2. postganglionic neurons have nicotinic receptors

3. effector organs have muscarinic receptors

B. Sympathetic (slide)

1. preganglionic neurons are cholinergic

2. postganglionic neurons are usually adrenergic

3. postganglionic neurons have nicotinic receptors

(quiz)

C. Autonomic balance
 
 

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Skeletal Muscle Contraction

Objectives:
The student should be able to:
1. Name the major proteins of the sarcomere that make up the thin and thick filaments.
2. Diagram how energy derived from ATP produces force through cross-bridge cycling.
3. Recognize that tension varies with the length of a muscle.
4. Name the neurotransmitter and its receptor type found at the neuromuscular junction.
5. Describe the role of the transverse tubule system.
6. State the key protein-ion interaction that initiates cross-bridge cycling.
7. List the anatomical, mechanical, and metabolic properties of slow and fast-twitch muscle fibers.
8. List two ways to produce a graded contraction.

Outline:
I. The Skeletal Muscle Motor Unit (slide)(slide)(animation)(slide)(animation)

A. One neuron innervates multiple muscle fibers.

B. Each muscle fiber receives innervation from only one neuron.

II. Excitation-Contraction (E-C) Coupling

A. Membrane depolarization and the action potential (slide)(quiz)

1. neurotransmitter is ACh
2. nicotinic receptor
3. graded depolarization spreads outside motor end-plate
4. action potential initiates outside the end-plate

B. Transverse-tubules (T-tubules) (slide)(quiz)

C. Coupling of the T-tubules and the terminal cisternae

1. triad complex of dihydropyridine (DHPR) receptor and ryanodine receptor (RyR)
2. AP sensed by DHPR
3. RyR allows calcium release from SR (animation)

D. The calcium cycle

1. calcium release by the SR
2. calcium binding by the troponin complex
3. cross-bridge cycling
4. uptake of calcium by the SR

III. Structural Organization of the Sarcomere (slide)

A. Z line-to-Z line is one sarcomere.

B. Thick filaments, or anisotropic regions (A-bands).

C. Thin filaments, or isotropic regions (I-bands).

D. Interdigitation of the filaments

E. Dynamics of the filaments during stretch and contraction (slide)(animation)

1. width of A-bands does not change
2. sarcomere lenght changes
3. therefore, I-band width changes
 

IV. The Sliding Filament Theory of Striated Muscle Contraction

A. Myosin and the thick filament (slide)

B. Actin, tropomyosin, and troponin and the thin filament

C. Myosin-actin cross-bridge cycling and the hydrolysis of ATP (slide)(slide)
(quiz)

V. The Length-Tension Relationship in Skeletal Muscle (slide)

A. Active tension

1. generated by myosin
2. consumes energy

B. Passive tension

1. connective tissue and intracellular structual proteins
2. does not consume energy

C. Length-tension relationship

D. Mechanical elements of muscle (slide)

E. Physico-chemical explanation of the length-tension relationship (slide)

1. at optimum sarcomere lengths, all mysoin heads can form cross-bridges
2. at long sarcomere lengths, some myosin heads cannot form cross-bridges
3. at short sarcomere lengths, too much stuff is trying to occupy too little space

F. At what position in the length-tension relationship do muscles operate? Skeletal muscle operates near the optimum sarcomere length.

VI.  The Twitch Mechanics of Contraction

A. Isometric contraction (slide)(animation)

1. one action potential
2. no shortening
3. TPT = time-to-peak tension
4. 1/2RT = half-relaxation time

B. Isotonic (shortening) contraction

1. load and the contractile apparatus (slide) (slide)(animation)(animation)(animation)
2. force-velocity relationship (slide)
3. maximal shortening velocity - Vmax

C. Muscle fiber-types and their mechanics (slide)  

VII. The Graded Contraction

A. The size principle and the hierarchy of recruitment (slide)

1. slow motor units are the first tobe recruited
2. successive motor units have faster characteristics
3. successive motor units have more fibers

B. The force-frequency relationship for tension development

1. summation and tetanus (slide) (slide)
2. facilitation

C. The graded contraction (slide)

D. Feedback and integration for control of force, velocity, and position

VIII. Energy and Fatigue

A. Turnover of ATP (slide)

1. velocity of contraction is related to ATP consumption
2. limited ATP stores are replenshed by creatine kinase

B. Muscle fiber-types and their metabolism (slide)

1. glycogenolytic metabolism
2. oxidative metabolism

(movie 2.4Mb)

C. Rigor
 

IX. Summary - The Spectrum of Motor Units and Their Recruitment (quiz)  

X. Adaptation - What do Astronauts and Hospital Patients Have in Common?

A. Exercise disrupts the milieu interieur

1. second messenger activity
2. metabolism

B.  Adaptational responses to training and detraining

1. acute responses - economy (slide)
2. chronic responses (slide)

a.  resistance work
b.  endurance work
c.  bedrest and hypokinesia

C. Muscle soreness

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Skeletal Muscle Mechanics, Smooth Muscle Contraction

Objectives:
The student should be able to:
1. Match the phases of shortening (isometric and isotonic) with the tension developed during these phases.
2. State the difference between syncytial and multi-unit smooth muscle.
3. State the electrical conditions that modulate smooth muscle contraction.
4. Name the type of innervation characteristic of smooth muscle.
5. List the key proteins that regulate smooth muscle contraction.
6. List the two ways to produce more force by smooth muscle.
 

Outline:
I. The Diversity of Smooth Muscle Function (slide)
 

II. Organization of Smooth Muscle (slide)

A. Smooth muscle cells are primarily mononuclear

B. Smooth muscles are mechanically and electrically diverse

1. Syncytial or "single-unit" smooth muscle (animation)

2. Multi-unit smooth muscle (animation)

C. Smooth muscle cells do not normally exhibit well-structured sarcomeres (slide)
(quiz)

III. Contractile Activity and its Regulation

A. The action potential and ion fluxes in smooth muscle

1. Membrane conductances are different from skeletal muscle (slide)

2. Calcium currents can play an important role (slide)

3. An action potential need not occur for contraction (slide)

4. Pacemaker activity causes spontaneous contraction (slide) (animation) (animation)

B. Nervous control of smooth muscle contraction (slide)

1. Innervation is exclusively autonomic

2. Modulation of contractile activation by nerves

a. excitatory effects

b. inhibitory effects

C. Non-neural control of smooth muscle contraction (slide)

1. Local and distant activation

2. Receptor-mediated and non-receptor mediated mechanisms

IV. Mechanism of Contraction of Smooth Muscle

A. Calcium and the permissive effect of myosin light chain-phosphorylation (slide)

1. Calcium-calmodulin interaction

2. Myosin light-chain kinase

3. Cross-bridge cycling

B. The central role of calcium and its various sources (slide)
(quiz)

C. Phosphatase activity and the cessation of cross-bridge cycling (slide)

(quiz)

D. The latch mechanism

E. The stress-relaxation mechanism (slide)

 
 

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Lower-Order Motor Control and Reflexes

Objectives:
The student should be able to:
1. Describe the role and innervation of excitatory and inhibitory interneurons.
2. Define the neurotransmitters involved in excitation and inhibition.
3. Identify which reflexes are monosynaptic.
4. State examples of reflexes of cutaneous and muscle origin.

Outline:
I. Signals impinging upon the a-motorneurons

A. Dorsal root ganglion (DRG) afferents from sensory nerves

1.  Excitatory (monosynaptic, i.e., direct synaptic connection) (slide)

2.  Inhibitory (polysynaptic, involve interneurons) (slide)

B. Higher motor centers

1.  Classification (slide)

a. intertract/intersegmental (propriospinal)

b. cerebellar

2.  Connections - all interneuron mediated

(quiz)

C. Renshaw cells - inhibitory interneurons to "focus" a response (slide)

II. DRG afferent nerve activity

A. Muscle spindle origin

B. Golgi tendon organ origin (slide)

C. Other proprioceptors

III. Circuits and connections

A. a-motorneuron efferent/sensory afferents (slide) (slide)

B. g-motorneuron efferent/sensory afferents (slide)

C. Propriospinal (intersegmental)

IV Reflexes

A. Myotatic (stretch) reflex (slide)

B.Golgi tendon reflex (slide)

C. Flexor reflex (slide) (animation)

D. Crossed extensor reflex (slide) (animation)

E. Other (stepping, gallop, scratch)(quiz)

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