SIGNAL TRANSDUCTION IN SMOOTH-MUSCLE AS STUDIED BY THE SUBCELLULAR MEMBRANE APPROACH

Many of the contractile regulatory events in smooth muscle reside in various cellular membrane components as functional membrane constituents that interact in a variably complex manner. The physiological handling of ionized calcium (Ca2+), which serves multiple roles as an extracellular signal, a second messenger, and an activator interacting directly with myofilaments to effectuate contractile responses, referred to as Ca2+ signalling processes, represents an integral part of a more complicated membrane transduction mechanism. The subcellular membrane approach toward the understanding of Ca2+ signalling as well as the transduction mechanisms involving membrane receptors, GTP binding proteins, ion channels, membrane-bound enzymes, and the production of intracellular second messengers has made a significant contribution in smooth muscle research for the past decade. This review summarizes the current state of knowledge about the multiplicity of interactions between Ca2+ and various membrane constituents in the surface membranes and sarcoplasmic reticulum, such as Ca2+ binding, Ca2+ ATPase pumps, Ca2+ channels, and Ca2+Na+ or related ion exchangers. A number of recent novel findings from this laboratory have also been discussed. First of all, the technical refinement of membrane separation and characterization, which permits better identification of neuronal membranes in highly innervated smooth muscle tissues, led to the distinction of prejunctional and postjunctional membrane receptors. Secondly, unlike the Ca2+-release channels labelled with [H-3]inositol 1,4,5-trisphosphate, the other type of internal membrane Ca2+-release channels labelled by [H-3]ryanodine has been identified only recently in smooth muscle. Thirdly, the successful use of thapsigargin and cyclopiazonic acid as selective inhibitors for the sarcoplasmic reticulum Ca2+ pump in smooth muscle provided novel pharmacological tools to probe the refilling mechanisms of internal Ca2+ stores. Finally, the intriguing relationship between, and regulation of, a-adrenoceptor subtypes in vascular smooth muscles underscores the complexity of their transducing mechanisms and associated utilization of Ca2+.