Chapter 29 - Electromechanical and Pharmacomechanical Coupling in Vascular Smooth Muscle Cells

Abstract

This chapter focuses on the various Ca2+ entry pathways and intracellular Ca2+ release mechanisms that contribute to the increase in [Ca2+]i, triggering the contraction of vascular smooth muscle. The L type—long-lasting or high voltage activated; single channel conductance 20–28 Ps—is the most predominant Ca2+ channel in smooth muscle cells, although the T type—transient or low voltage activated; single channel conductance 7–15 pS—has also been observed in a number of smooth muscle cell preparations. Expression of the L-type Ca2+ channel depends on the differentiated state of vascular smooth muscle cells, as the current is decreased significantly in dedifferentiated A7r5 cells and increased upon differentiation with retinoic acid. L-type voltage-dependent Ca2+ channels are modulated not only by vasoactive agonists, but also by extracellular pH, PO2, and blood pressure. Vasoactive agonists also activate additional Ca2+ entry pathways, either directly or via generation of second messengers, or via depletion of IP3-sensitive Ca2+ stores. IP3R seems to be the major pathway for Ca2+ release during pharmacomechanical coupling. Smooth muscle cells also express ryanodine receptors and they also contribute to the shaping of the intracellular Ca2+ signal. There are three different types of IP3R, and it is becoming increasingly evident that functional differences exist between these isoforms, including differences in redox sensitivity, in ATP sensitivity, and possibly also in Ca2+ sensitivity.