Introduction

The obligatory role of Ca2+ in muscle contraction was first described by Ringer (1882), and subsequently Ca2+ was shown to stimulate a host of regulatory enzymes. The change in intracellular free Ca2+ necessary for contraction is very small, on the order of 1 μM. This chapter deals with the variety of organelles, regulatory factors, and mechanisms that work together to maintain this tight control of the intracellular free Ca2+ concentration in smooth muscles.

Overview

The control of intracellular free Ca2+ concentration was first explored in skeletal and cardiac muscles. Now, knowledge of events in smooth muscles is also progressing rapidly. Major quantitative and qualitative differences between skeletal and smooth muscles are evident. Whereas in skeletal muscle Ca2+ flux and contraction are initiated by Na+ influx and membrane depolarization, in smooth muscles Ca2+ translocation and contraction can occur independently of changes in membrane potential (Edman and Schild 1963). This phenomenon, called pharmacomechanical coupling (Somlyo and Somlyo 1968), can be initiated by agonist receptor binding, release of second messengers, release of Ca2+ from internal stores, or opening of receptor-operated Ca2+ channels. Influx of Ca2+ through Ca2+ channels is very important for tension development in smooth muscles, but not in skeletal muscle.

Although smooth muscles resemble each other more than they do cardiac or skeletal muscles, major differences are evident in the structures and functions among different smooth muscles. These differences may be determined by the number and specificity of receptors, the second messengers generated, the Ca2+ pathway involved, and the activity of Ca2+−sensitive enzymes including the protein kinases.