Diseases such as hypertension and diabetes appear to affect ion channel expression or function and contribute to altered arteriolar tone associated with these pathologies. In hypertension there appears to be an upregulation of voltage-gated Ca2+ channels, nonselective cation channels, and BKCa channels, but decreased function of KV and KATP channels that likely contribute to altered arteriolar tone and reactivity observed in this disease. Similarly, in diabetes there is a depression of BKCa, KV, and KATP channel function that may contribute to diabetic vascular dysfunction. Conversely, sepsis is associated with a large increase in the activity KATP channels that may underlie the systemic vasodilation and reduced arteriolar tone associated with this condition. Thus, ion channels participate in both physiological and pathophysiological regulation of arteriolar tone.
Depolarization: Refers to cell membrane potential becoming more positive.
Electrochemical gradient: The driving force that determines the direction of net diffusion of ions through ion channels. Its magnitude is determined by the difference between the cell membrane potential (which determines the electrical force on the ion) and the concentration difference for the ion that exists across the membrane (which determines the chemical "force" on the ion). Its magnitude can be calculated as the difference between the membrane potential and the equilibrium potential for a given ion.
Equilibrium potential: Theoretical membrane potential that would be required to exactly oppose diffusion of an ion down a given concentration gradient. It is also referred to as the Nernst potential.
Hyperpolarization: Refers to cell membrane potential becoming more negative.
Myoendothelial gap junctions: Gap junctions between endothelial cells and smooth muscle cells that allow ions and small molecules to diffuse between the two cell types. They allow electrical activity in one cell type to be transmitted to the other cell type.
Archer, S. L., and Rusch, N. J., eds. (2001). Potassium Channels in Cardiovascular Biology. New York: Kluwer Academic/Plenum. This is an outstanding compilation of in-depth reviews of K+ channels in the cardiovascular system. Very comprehensive treatment from the molecular and structural biology of K+ channels to their function and pharmacology. Recommended reading for anyone interested in K+ channels and the cardiovascular system. Beech, D. J., Xu, S. Z., McHugh, D., and Flemming, R. (2003). TRPC1 store-operated cationic channel subunit. Cell Calcium 33(5-6), 433-440.
Busse, R., Edwards, G., Feletou, M., Fleming, I., Vanhoutte, P. M., and Weston, A. H. (2002). EDHF: Bringing the concepts together. Trends Pharmacol. Sci. 23(8), 374-380. An outstanding brief synopsis of endothelium-dependent hyperpolarization of vascular smooth muscle, and the role played by sKCa and IKca channels in this process. Hille, B. (2001). Ionic Channels of Excitable Membranes. Sunderland, MA: Sinauer. This is an excellent, comprehensive overview of all types of ion channels, membrane physiology, and biophysics. It provides a very good starting point to learn about ion channels and their function. Jackson, W. F. (2000). Ion channels and vascular tone. Hypertension
35(1, Pt. 2), 173-178. Jaggar, J. H., Porter, V. A., Lederer, W. J., and Nelson, M. T. (2000). Calcium sparks in smooth muscle. Am. J. Physiol. Cell Physiol. 278(2), C235-256.
Jentsch, T. J., Stein, V., Weinreich, F., and Zdebik, A. A. (2002). Molecular structure and physiological function of chloride channels. Physiol Rev. 82(2), 503-568.
Keef, K. D., Hume, J. R., and Zhong, J. (2001). Regulation of cardiac and smooth muscle Ca(2+) channels (Ca(V)1.2a,b) by protein kinases. Am. J. Physiol. Cell Physiol. 281(6), C1743-1756. Nilius, B., and Droogmans, G. (2001). Ion channels and their functional role in vascular endothelium. Physiol Rev. 81(4), 1415-1459. An excellent review of ion channels and their physiological function in endothe-lial cells. Provides a good overview of signaling in endothelial cells and the role played by ion channels in this process. Welsh, D. G., Morielli, A. D., Nelson, M. T., and Brayden, J. E. (2002). Transient receptor potential channels regulate myogenic tone of resistance arteries. Circ. Res. 90, 248-250. This is the landmark study demonstrating that TRPC 6 likely underlies SAC in smooth muscle.
Dr. Jackson is a professor in the Department of Biological Sciences at Western Michigan University and in 1998 won the Distinguished Faculty Scholar Award, Western's highest honor for research accomplishments. His laboratory focuses on ion channel function and expression in arterioles, their modulation by oxygen, and their function in regulation of microvas-cular blood flow. Dr. Jackson's research is supported by Public Health Service grant HL 32469 from the National Heart, Lung and Blood Institute.
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