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K Membrane potential is a principal regulator of arterial contractility. Arterial smooth muscle cells express several different types of ion channel that control membrane potential, including KV channels. KV channel activation leads to membrane hyperpolarization, resulting in inhibition of voltage-dependent Ca2+ channels, a reduction in [Ca2+ ]i , and vasodilation. In contrast, KV channel inhibition leads to membrane depolarization and vasoconstriction. The ability of KV channels to regulate arterial contractility is dependent upon the number of plasma membrane-resident channels and their open probability. Here, we will discuss mechanisms that alter the surface abundance of KV channel proteins in arterial smooth muscle cells and the functional consequences of such regulation. Cellular processes that will be described include those that modulate KV channel transcription, retrograde and anterograde trafficking, and protein degradation.

K VSMCs in resistance arteries and arterioles express a diverse array of KV channels with members of the KV 1, KV 2 and KV 7 families being particularly important. Members of the KV channel family: (i) are highly expressed in VSMCs; (ii) are active at the resting membrane potential of VSMCs in vivo (-45 to -30 mV); (iii) contribute to the negative feedback regulation of VSMC membrane potential and myogenic tone; (iv) are activated by cAMP-related vasodilators, hydrogen sulfide and hydrogen peroxide; (v) are inhibited by increases in intracellular Ca2+ and vasoconstrictors that signal through Gq -coupled receptors; (vi) are involved in the proliferative phenotype of VSMCs; and (vii) are modulated by diseases such as hypertension, obesity, the metabolic syndrome and diabetes. Thus, KV channels participate in every aspect of the regulation of VSMC function in both health and disease.