Signaling between SR and plasmalemma in smooth muscle: sparks and the activation of Ca 2+-sensitive ion channels

Abstract

Intracellular calcium ions are involved in the regulation of nearly every aspect of cell function. In smooth muscle, Ca 2+ can be delivered to Ca 2+-sensitive effector molecules either by influx through plasma membrane ion channels or by intracellular Ca 2+ release events. Ca 2+ sparks are transient local increases in intracellular Ca 2+ that arise from the opening of ryanodine-sensitive Ca 2+ release channels (ryanodine receptors) located in the sarcoplasmic reticulum. In arterial myocytes, Ca 2+ sparks occur near the plasma membrane and act to deliver high (μM) local Ca 2+ to plasmalemmal Ca 2+-sensitive ion channels, without directly altering global cytosolic Ca 2+ concentrations. The two major ion channel targets of Ca 2+ sparks are Ca 2+-activated chloride (Cl Ca) channels and large-conductance Ca 2+-activated potassium (BK) channels. The activation of BK channels by Ca 2+ sparks play an important role in the regulation of arterial diameter and appear to be involved in the action of a variety of vasodilators. The coupling of Ca 2+ sparks to BK channels can be influenced by a number of factors including membrane potential and modulatory β subunits of BK channels. Cl Ca channels, while not present in all smooth muscle, can also be activated by Ca 2+ sparks in some types of smooth muscle. Ca 2+ sparks can also influence the activity of Ca 2+-dependent transcription factors and expression of immediate early response genes such as c- fos. In summary, Ca 2+ sparks are local Ca 2+ signaling events that in smooth muscle can act on plasma membrane ion channels to influence excitation–contraction coupling as well as gene expression.