Regulation of Calcium Sensitivity in Vascular Smooth-Muscle

Abstract

Calcium ions (Ca²⁺) play a pivotal role in musde contraction in that they regulate events that result in excitation-contraction coupling. The concept has emerged that signaling at the membrane of arteries and veins—for example, by receptor stimulation and depolarization—leads to a decrease in the approx 10,000-fold electrochemical gradient for Ca²⁺, ostensibly by increasing the permeability to extracellular Ca²⁺ and by mobilizing intracellular stores of Ca²⁺. 1-3 The mechanisms whereby activation of voltage, receptor, and stretch-operated Ca²⁺ channels lead to entry of extracellular Cat+ is discussed elsewhere in this volume, as is the electrical coupling of vascular smooth-muscle cells. In this chapter we discuss recently obtained evidence on the regulation of intracellular sensitivity to Ca²⁺, based primarily on evidence obtained in vascular preparations that may not be representative of resistance arteries. 4,5 Although specialization such as neurovascular transmission, 6 altered receptor pharmacology, 7 mechanical activation of myogenic characteristics 8 and regulation of transmitter release 9 occurs in arteries of diminishing size, it remains to be determined whether intracellular mechanisms regulating vascular tone are also differentially regulated in resistance arteries.