Cell calcium and its regulation in smooth muscle

Abstract

Two novel methods used to study smooth muscles — electron probe X‐ray microanalysis and Ca 2+ ‐sensitive indicators (which are used for resolving, respectively, the spatial distribution and temporal distribution of calcium) — are briefly reviewed and the major findings obtained are summarized. In smooth muscle the sarcoplasmic reticulum is the major intracellular source of Ca 2+ ; mitochondria do not play a significant role in the physiological regulation of [Ca 2+ ] i . Under pathological conditions mitochondria can reversibly accumulate large amounts of calcium. Resting [Ca 2+ ] i generally ranges from 80 to 200 nM, and is lower in phasic than in tonic smooth muscles. Removal of extracellular Ca 2+ and Ca 2+ entry blockers can reduce [Ca 2+ ] i , but the effects of β‐adrenergic agents are variable. Increases in [Ca 2+ ] i are triggered by electrical stimulation, depolarization with high K + , and excitatory agonists. Stretch, after a delay of several seconds, can cause an increase in [Ca 2+ ] i in some smooth muscles. There is also a delay of approximately 200‐400 ms between the initiation of the rise of Ca 2+ and contraction that follows spontaneous action potentials or electrical stimulation. Agonist‐induced Ca 2+ release, a major mechanism of pharmacomechanical coupling, has been demonstrated in smooth muscles depolarized with high K; evidence suggests that it is mediated by G proteins that couple receptors to phospholipase C. Ca 2+ release can be triggered directly in permeabilized smooth muscle with inositol 1,4,5‐trisphosphate. Even though Ca 2+ is the major physiological regulator of contraction, Ca 2+ sensitivity of the regulatory‐contractile apparatus differs in different (phasic and tonic) smooth muscles, and can be modulated in a given smooth muscle. The force [Ca 2+ ] i ratio is higher during agonist‐stimulated than during high K + ‐induced contractions, owing to agonist‐induced increases in Ca 2+ sensitivity mediated by G proteins. In some phasic smooth muscles (guinea pig ileum), the time course of the initial myosin light chain phosphorylation is extremely rapid and returns to basal levels while force remains elevated. In these smooth muscles there is also a marked decrease in the Ca 2+ sensitivity of the regulatory‐contractile apparatus during maintained depolarization in Ca 2+ ‐free or low Ca 2+ solutions. It has been suggested that regulation of myosin light chain phosphatase plays a major role in the modulation of the Ca 2+ sensitivity manifested as either potentiation or desensitization to [Ca 2+ ] i .—S omlyo , A. P.; H impens , B. Cell calcium and its regulation in smooth muscle. FASEB J. 3: 2266‐2276; 1989.