Cell calcium and its regulation in smooth muscle

Abstract

Two novel methods used to study smooth muscles-electron probe X-ray microanalysis and Ca2+-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 Ca2+; mitochondria do not play a significant role in the physiological regulation of [Ca2+]i. Under pathological conditions mitochondria can reversibly accumulate large amounts of calcium. Resting [Ca2+]i generally ranges from 80 to 200 nM, and is lower in phasic than in tonic smooth muscles. Removal of extracellular Ca2+ and Ca2+ entry blockers can reduce [Ca2+]i, but the effects of beta-adrenergic agents are variable. Increases in [Ca2+]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 [Ca2+]i in some smooth muscles. There is also a delay of approximately 200-400 ms between the initiation of the rise of Ca2+ and contraction that follows spontaneous action potentials or electrical stimulation. Agonist-induced Ca2+ 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. Ca2+ release can be triggered directly in permeabilized smooth muscle with inositol 1,4,5-trisphosphate. Even though Ca2+ is the major physiological regulator of contraction, Ca2+ 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 [Ca2+]i ratio is higher during agonist-stimulated than during high K+-induced contractions, owing to agonist-induced increases in Ca2+ 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 Ca2+ sensitivity of the regulatory-contractile apparatus during maintained depolarization in Ca2+-free or low Ca2+ solutions. It has been suggested that regulation of myosin light chain phosphatase plays a major role in the modulation of the Ca2+ sensitivity manifested as either potentiation or desensitization to [Ca2+]i.

Calcium Signaling in Airway Smooth Muscle

“…These observations indicate that the basal intracellular calcium level influences the kinetics of the calcium oscillations. In smooth muscle cells, the basal [Ca 21 ] i under unstimulated conditions is approximately 200 nM, and exposure to contractile agonists increases this level in a concentration-dependent fashion (10,11). Therefore, we predicted that there would be agonist concentration-dependent changes in the frequency and propagation velocity of the calcium oscillations.…”

High K+-induced contraction requires depolarization-induced Ca2+ release from internal stores in rat gut smooth muscle

“…Smooth muscle contraction is widely accepted to be triggered by a rise in cytosolic free Ca 2+ concentration ([Ca 2+ ] i ), which is regulated by either pharmacomechanical coupling to agonists that induce contraction without membrane depolarization, or by membrane depolarization itself in a process known as electromechanical coupling [1][2][3] . The rise in [Ca 2+ ] i leads to calmodulin-dependent activation of myosin light chain kinase (MLCK) and results in the phosphorylation of the 20-kDa light chain of myosin [4,5] .…”

Ca2+ clearance in smooth muscle: lessons from gene-altered mice

“…The nature and relative contribution of these various components of cytosolic Ca 2+ clearance have long been an important topic for study in smooth muscle (Casteels et al, 1986;Rüegg, 1988;Somlyo and Himpens, 1989;Daniel et al, 1995;Karaki et al, 1997;Zderic et al, 1999;Sanders, 2001;Karaki, 2004).…”