Calcium Events in Smooth Muscles and Their Associated Cells

Abstract

Calcium is essential for contraction of smooth muscle cells (SMC). The contractile proteins are activated by calcium released from the stores within the cell in response to calcium entry through voltage-dependent channels and/or activation of receptors, which often increase D-myoinositol 1,4,5-trisphosphate (IP3) concentration in the cell through stimulation of phospholipase C (PLC). A global rise in the concentration of ionized calcium, [Ca2+] i , which gives rise to contraction or shortening, is initiated at preferred locations in the cell, termed frequent discharge sites (FDS). In many SMC these sites often spontaneously discharge calcium packets; this is caused by bursts of openings of calcium channels (commonly ryanodine receptors, RyR, or IP3 receptors) in the sarcoplasmic reticulum (SR). The rise in [Ca2+] i may be detected by introducing calcium indicator dyes into the cell; the release of a calcium packet then gives rise to a rapid increase in fluorescence, or “spark.” A spark may activate a burst of openings of calcium-activated potassium or chloride channels in the cell membrane, so giving rise to spontaneous transient outward currents (STOC) or spontaneous transient inward currents (STIC), respectively. The term “spark” should probably be reserved for a calcium event resulting from the discharge of a single cluster, or domain, of RyR channels; when IP3; concentrations are raised, adjacent domains may discharge closely in time, giving rise to larger calcium events, activation of more distant domains by a fire-diffuse-fire mechanism, and saltatory propagation of a calcium wave leading to a global rise in [Ca2+] i and contraction of the cell. In many smooth muscle tissues, including some blood vessels, SMC are associated with interstitial cells (IC); well-known examples are the IC of Cajal in the gut muscles. In the media of small mesenteric arteries and portal vein, the IC share many properties with the SMC but, unlike the latter, have many thin processes and do not contract to agents, which contract the SMC. The role of these IC in blood vessels is unknown.