Calcium sparks in smooth muscle

Local intracellular Ca²⁺transients, termed Ca²⁺ sparks, are caused by thecoordinated opening of a cluster of ryanodine-sensitive Ca²⁺ release channels in the sarcoplasmic reticulum ofsmooth muscle cells. Ca²⁺ sparks are activated byCa²⁺ entry through dihydropyridine-sensitivevoltage-dependent Ca²⁺ channels, although the precisemechanisms of communication of Ca²⁺ entry toCa²⁺ spark activation are not clear in smooth muscle.Ca²⁺ sparks act as a positive-feedback element to increasesmooth muscle contractility, directly by contributing to the globalcytoplasmic Ca²⁺ concentration([Ca²⁺]) and indirectly by increasingCa²⁺ entry through membrane potential depolarization,caused by activation of Ca²⁺ spark-activatedCl channels. Ca²⁺ sparks also have aprofound negative-feedback effect on contractility by decreasingCa²⁺ entry through membrane potential hyperpolarization,caused by activation of large-conductance, Ca²⁺-sensitiveK⁺ channels. In this review, the roles of Ca²⁺sparks in positive- and negative-feedback regulation of smooth musclefunction are explored. We also propose that frequency and amplitudemodulation of Ca²⁺ sparks by contractile and relaxantagents is an important mechanism to regulate smooth muscle function.