Exercise and Ion-Channel Remodeling in Vascular Smooth Muscle During Hypertension: Therapeutic Implications

Abstract

Myogenic contraction of vascular smooth muscle cells (VSMCs) in resistance arteries and arterioles plays a critical role in regulating peripheral resistance. Ion channels expressed in VSMCs control ion influx or efflux from the plasma membrane and endoplasmic reticulum to regulate membrane potential, which contributes to the regulation of vascular tone. With the depolarization of VSMC membranes, an elevation of intracellular calcium ion (Ca 2+) concentration is mediated by voltagegated Ca 2+ channels and can trigger a vasoconstrictive response. In addition, potassium ion (K +) efflux through K + channels can hyperpolarize VSMCs, resulting in vasodilation. However, in the pathophysiological progression of diseases such as hypertension, VSMCs undergo a wide range of pathological changes, among them is "electrical remodeling", which refers to changes in ion channels. Under physiological or pathological conditions, exercise has a profound impact on the human body, and ion channels are an essential target of the beneficial adaptive responses. This review provides insight on the physiological function of ion channels in VSMCs, including Ca V 1.2 channels, voltage-gated K + channels, large-conductance Ca 2+-activated K + channels, and inward-rectifier K + channels, and the changes of these ion channels during hypertension. Focus is given to the effects of exercise on these ion channels and its implications in disease treatment.