Induction of Ca2+ -Activated K+ Channel Expression during Systemic Hypertension: Protection against Pathological Vasoconstriction
During the past 15 years, patch-clamp studies have characterized a diverse population of K+ channel types in vascular smooth muscle cells. Prominent among these is the high-conductance, Ca2+ -activated K+ channel (BKCa channel), which appears to be ubiquitously expressed in arterial smooth muscle membranes. The BKCa channel in some vascular beds may act together with other K+ channel types to set the level of resting membrane potential in the arterial smooth muscle cells. During vascular excitation, the further activation of BKCa channels may provide a powerful pathway to hyperpolarize the arterial smooth muscle cells, thereby limiting voltage-gated Ca2+ influx and buffering vasoconstriction in small arteries and resistance vessels. Thus, under physiological conditions, the BKCa channel acts as a homeostatic mechanism to counteract arterial constriction and maintain blood flow to critical organs and tissues.
KeywordsPermeability Ischemia Barium Angiotensin Norepinephrine
Unable to display preview. Download preview PDF.
- Berger, M. G., and Rusch, N. J., 1999, Voltage and calcium-gated potassium channels: Functional expression and therapeutic potential in the vasculature, in: Perspectives in Drug Discovery and Design (J. M. Sabatier and H. Darbon, eds.), Kluwer Academic, Dordrecht, The Netherlands, Vol. 15/16, pp. 313–332.Google Scholar
- Dopica, A. M., Kirber, M. T., Singer, J. J., and Walsh, J. V., 1994, Membrane stretch directly activates large conductance Ca2+-activated K+ channels in mesenteric artery smooth muscle cells, Am. J. Hypertens. 7:82–89.Google Scholar
- Garwitz, E. T., and Jones, A. W., 1982b, Altered arterial ion transport and its reversal in the aldosterone hypertensive rat, Am. J. Physiol. 243:H929–H933.Google Scholar
- Jones, A. W., 1983, Arterial tissue cations, in: Hypertension, Physiology and Treatment (J. Genest, O. Kuchel, P. Hamet, and M. Cantin, eds.), McGraw-Hill, New York, pp. 488–497.Google Scholar
- Kolias, T. J., Chai, S., and Webb, R. C, 1993, Potassium channel antagonists and vascular reactivity in stroke-prone spontaneously hypertensive rats, Am. J. Hypertens. 23:1077–1082.Google Scholar
- Lagrutta, A., Shen, K., North, R. A., and Adelman, J. P., Functional differences among alternatively spliced variants of Slowpoke, a Drosophila calcium-activated potassium channel, J. Biol. Chem. 269:20347–20351.Google Scholar
- Papp, B., Corvazier, E., Magnier, C., Kovacs, T., Bourdeau, N., Levy-Toledano, S., Bredoux, R., Levy, B., Poitevin, P., Lompre, A. M., Wuytack, F., and Enouf, J., 1993, Spontaneously hypertensive rats and platelet Ca2+-ATPases: Specific upregulation of the 97-kDa isoform, Biochem. J. 295:685–690.PubMedGoogle Scholar
- Rusch, N. J., and Hermsmeyer, K., 1993, Vascular muscle calcium channels in hypertension, in: Ionic Transport in Hypertension: New Perspectives (A. Coca, ed.), CRC Press, Boca Raton, Florida, pp. 197–227.Google Scholar
- Sickowski, M., Davies, D. E., and Ng, L. L., 1994, Sodium-hydrogen antiporter protein in normotensive Wistar-Kyoto rats and spontaneously hypertensive rats, J. Hypertens. 12:775–781.Google Scholar