Smooth muscle occurs in many tissues and has to fulfil different roles depending upon its location, e.g. tonic force in many blood vessels and phasic activity in most viscera. While it is well understood that a rise of intracellular [Ca] is associated with smooth muscle activity, and smooth muscles have an intracellular Ca store in the SR, the precise details of Ca signalling and the role of the SR remain to be elucidated. In this presentation details of the mechanisms and the differences between different smooth muscles will be examined in uterine and ureteric myocytes.
Most smooth muscles possess both IP3 and ryanodine receptors on their SR membrane. It was therefore assumed that both agonist-induced, and Ca-induced Ca release (IICR and CICR, respectively) would play roles in augmenting force production. Interestingly there are few examples of CICR playing any role in this process. The coupling between Ca entry and the ryanodine receptor appears therefore to be a lot looser in smooth muscle than cardiac muscle. The role overall of the SR may differ in smooth compared with striated muscles, in that its main function appears to be as a break on contraction rather than a stimulator. For example, in uterine muscle inhibition of the SR, by emptying with cyclopiazonic acid, increases both the frequency and amplitude of contractions rather than reducing force. The Ca released from the SR appears to be vectorially targeted at surface membrane ion channels, rather than the contractile proteins. In vascular smooth muscle there is excellent evidence that SR Ca release activates K channels, and thereby contributes to vasorelaxation. This may be the mechanism operating in the uterine myocytes.
In ureteric smooth muscles we have found that there is a clear species difference in the control of the SR. Thus in rats a purely IICR mechanism operates, whereas in the guinea-pig it is a CICR system. We are exploiting this difference to explore the fundamental properties of the local release mechanisms (puffs and sparks) in the two species and how they relate to global signalling. These data will be discussed along with the corresponding electrophysiological events. We will also discuss how simultaneous direct measurements of SR and cytoplasmic [Ca] are increasing our understanding of the control of SR Ca release and its relation to cytosolic [Ca], but also raising questions concerning SR Ca availability and the relation of the SR to mitochondria.