Invited Review Regulation of smooth muscle calcium sensitivity: KCl as a calcium- sensitizing stimulus

00529.2004.—KCl has long been used as a convenient stimulus to bypass G protein-coupled receptors (GPCR) and activate smooth muscle by a highly repro-ducible and relatively “simple ” mechanism involving activation of voltage-oper-ated Ca2 channels that leads to increases in cytosolic free Ca2 ([Ca2]i), Ca2-calmodulin-dependent myosin light chain (MLC) kinase activation, MLC phosphorylation and contraction. This KCl-induced stimulus-response coupling mechanism is a standard tool-set used in comparative studies to explore more complex mechanisms generated by activation of GPCRs. One area where this approach has been especially productive is in studies designed to understand Ca2 sensitization, the relationship between [Ca2]i and force produced by GPCR agonists. Studies done in the late 1980s demonstrated that a unique relationship between stimulus-induced [Ca2]i and force does not exist: for a given increase in [Ca2]i, GPCR activation can produce greater force than KCl, and relaxant agents can produce the opposite effect to cause Ca2 desensitization. Such changes in Ca2 sensitivity are now known to involve multiple cell signaling strategies