Research Interest

The focus of the laboratory is to study mechanisms that regulate the diameter of small arteries and arterioles that modulate systemic blood pressure and organ blood flow.  Smooth muscle cells within the vascular wall determine arterial diameter.  Thus, our major focus is to investigate the functional significance of arterial smooth muscle cell plasma membrane and intracellular ion channels and local and global calcium signals in regulating arterial smooth muscle cell contractility.  Research in the laboratory involves a multi-faceted approach, studying events at molecular, cellular and intact artery levels.  Techniques include patch clamp electrophysiology, rapid confocal calcium imaging, conventional calcium imaging, diameter measurement of pressurized arteries, use of knockout models, and molecular biology.  Please click on My Laboratory for more detailed information.

Research Support

04/01/08 - 03/31/13, NIH R01 HL67061, Calcium Signaling in Cerebral Arteries. P.I.
07/01/09 - 06/01/14, NIH R01 HL94378, Calcium Channels in Arterial Smooth Muscle Cells. P.I.
04/01/05 - 03/28/10, NIH R01 HL77678, Mitochondrial Regulation of Calcium Signaling and Diameter in Cerebral Arteries. P.I.
04/01/85 - 03/31/12, NIH R01 HL34059, Carbon Monoxide in Newborn Circulation, Co-I.
08/01/91 - 07/01/10, NIH R01 HL42851, Control of Neonatal Circulation, Co-I.
07/01/09 - 06/01/14, NIH R01 AA11560, Ethanol Actions on Slo1 Channels from Arteries versus Brain. Co-I.

Selected Publications

1. Jaggar JH. Intravascular pressure regulates local and global calcium signaling in cerebral artery smooth muscle cells. Am J Physiol 2001; 281:C439-C448.
2. Jaggar JH,  Leffler CW,  Cheranov SY,  Tcheranova D,  ES,  Cheng X. Carbon monoxide dilates cerebral arterioles by enhancing the coupling of Ca²⁺ sparks to Ca²⁺-activated K⁺ channels. Circ Res 2002; 91: 610-617.
3. Cheranov SY, Jaggar JH. Sarcoplamic reticulum calcium load regulates rat arterial smooth muscle calcium sparks and transient K_Ca currents.  J Physiol 2002; 544:71-84.
4. Cheranov SY, Jaggar JH. Mitochondrial modulation of Ca²⁺ sparks transient K_Ca currents in smooth muscle cells of rat cerebral arteries. J Physiol 2004; 556:  755-771.
5. Liu P, Xi Q, Ahmed A, Jaggar JH, Dopico AM. Essential role for smooth muscle BK channels in alcohol-induced cerebrovascular constriction.  Proc Natl Acad Sci USA. 2004; 101:18217-18222.
6. Xi Q, Cheranov SY,  Jaggar JH. Mitochondria-derived reactive oxygen species dilate cerebral arteries by activating Ca²⁺ sparks.  Circ Res 2005; 97:354-362.
7. Jaggar JH, Li A, Parfenova H, Liu J., Umstot ES, Dopico AM, Leffler CW. Heme is a carbon monoxide receptor for large-conductance Ca²⁺-activated K⁺ channels.  Circ Res 2005; 97: 805-812.
8. Cheranov, SY and Jaggar, J H.  TNF-alpha dilates cerebral arteries via NAD(P)H oxidase-dependent Ca²⁺ spark activation.  Am J Physiol. 2006; 290:C964-C971.
9. Cheng, X, Liu, J, Asuncion-Chin, M, Blaskova, E, Bannister, JP, Dopico, AM and Jaggar JH.  A novel Ca_V1.2 N-terminus expressed in smooth muscle cells of resistance-size arteries modifies channel regulation by auxiliary subunits.  J Biol Chem. 2007; 282: 29211-29221.
10. Li, A, Xi, Q, Umstot, ES, Bellner, L, Laniado-Schwartzman, M, Jaggar, JH, and Leffler, CW. Astrocyte-derived CO is a diffusible messenger that mediates glutamate-induced cerebral arteriolar dilation by activating smooth muscle cell K_Ca channels.  Circ Res. 2008;102(2):234-41.
11. Xi, Q, Adebiyi, A, Zhao, G, Chapman, KE, Waters, CM, Hassid, A, and Jaggar, JH.  IP₃ constricts cerebral arteries via IP₃ receptor-mediated TRPC3 channel activation and independently of sarcoplasmic reticulum Ca²⁺ release. Circ Res. 2008; 102(9): 1118-1126.
12. Adebiyi, A., McNally, E.M., and Jaggar, J.H.  Sulphonylurea receptor-dependent and -independent pathways mediate vasodilation induced by K_ATP channel openers.  Mol Pharmacol. 2008; 74: 736-743
13. Zhao, G., Adebiyi, A., Blaskova, E., Xi, Q., and Jaggar, J.H. Type 1 inositol 1,4,5-trisphosphate receptors mediate UTP-induced cation currents, Ca²⁺ signals, and vasoconstriction in cerebral arteries. Am J Physiol. 2008; 295(5):C1376-84.
14.  Cheng X., Pachuau J., Blaskova E., Asuncion-Chin M., Liu J., Dopico A.M., Jaggar J.H. Alternative splicing of Ca_V1.2 channel exons in smooth muscle cells of resistance-size arteries generates currents with unique electrophysiological properties. Am. J. Physiol. 2009; 297: H680-H688.
15. Bannister, J.P., Adebiyi, A., Zhao, G., Narayanan, N., Thomas, C.M., Feng, J.Y.,  Jaggar, J.H. Smooth muscle cell alpha₂delta-1 subunits are essential for vasoregulation by Ca_V1.2 channels.  Circ. Res. 2009; 105: 948-955.