New expression profiles of voltage-gated ion channels in arteries exposed to high blood pressure.
The diameters of small arteries and arterioles are tightly regulated by the dynamic interaction between Ca(2+) and K(+) channels in the vascular smooth muscle cells. Calcium influx through voltage-gated Ca(2+) channels induces vasoconstriction, whereas the opening of K(+) channels mediates hyperpolarization, inactivation of voltage-gated Ca(2+) channels, and vasodilation. Three types of voltage-sensitive ion channels have been highly implicated in the regulation of resting vascular tone. These include the L-type Ca(2+) (Ca(L)) channels, voltage-gated K(+) (K(V)) channels, and high-conductance voltage- and Ca(2+)-sensitive K(+) (BK(Ca)) channels. Recently, abnormal expression profiles of these ion channels have been identified as part of the pathogenesis of arterial hypertension and other vasospastic diseases. An increasing number of studies suggest that high blood pressure may trigger cellular signaling cascades that dynamically alter the expression profile of arterial ion channels to further modify vascular tone. This article will briefly review the properties of Ca(L), K(V), and BK(Ca) channels, present evidence that their expression profile is altered during systemic hypertension, and suggest potential mechanisms by which the signal of elevated blood pressure may result in altered ion channel expression. A final section will discuss emerging concepts and opportunities for the development of new vasoactive drugs, which may rely on targeting disease-specific changes in ion channel expression as a mechanism to lower vascular tone during hypertensive diseases.
Cox
Robert H
RH
Lankenau Institute for Medical Research, Jefferson Health System, Philadelphia, PA, USA.
Rusch
Nancy J
NJ
D001158:Arteries / Q000737:chemistry / Q000503:physiopathology; D015220:Calcium Channels / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D025461:Feedback, Physiological / Q000502:physiology*; D006439:Hemodynamics; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000503:physiopathology; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology
D015220:Calcium Channels; D024642:Potassium Channels, Voltage-Gated