Calcium Channels in Vascular Smooth Muscle

Abstract

Calcium (Ca²⁺) plays a central role in excitation, contraction, transcription, and proliferation of vascular smooth muscle cells (VSMs). Precise regulation of intracellular Ca²⁺ concentration ([Ca²⁺]_i) is crucial for proper physiological VSM function. Studies over the last several decades have revealed that VSMs express a variety of Ca²⁺-permeable channels that orchestrate a dynamic, yet finely tuned regulation of [Ca²⁺]_i. In this review, we discuss the major Ca²⁺-permeable channels expressed in VSM and their contribution to vascular physiology and pathology.

Keywords: Arteries; Ca(2+) signaling; Contraction; Ion channels; Myogenic tone; Sarcoplasmic reticulum.

Fig. 1

Schematic representation of the interplay of major Ca²⁺-permeable channels involved in the regulation of VSM [Ca²⁺]_i and contractility. Ca²⁺ influx predominantly through L-type Ca_V1.2 and to some extent T-type Ca_V3.1/3.3 channels promotes VSM contraction. L-type CaV1.2 and T-type Ca_V3.1/3.3 channel activity can be regulated, via membrane potential, by several Ca²⁺-permeable channels serving (1) depolarizing and (2) hyperpolarizing roles, thus modulating the contractile state of VSM. The emerging role of mitochondria Ca²⁺ channels in regulation of VSM Ca²⁺ homeostasis and vascular reactivity is not depicted in this cartoon for simplicity. (+) denotes positive modulation, (−) represents negative modulation, and (?) indicates areas of uncertainty in the pathway.