A, activation of Ca2+-activated K+ channels by Ca2+ sparks results in spontaneous transient outward currents (STOCs), hyperpolarizing the plasma membrane (increased membrane potential; Vm). This reduces activation of voltage-operated Ca2+ channels (VOCCs), decreasing Ca2+ influx and global [Ca2+]. This can act as a negative feedback mechanism, whereby localized Ca2+ release from the sarcoplasmic reticulum (SR) lowers mean cytosolic [Ca2+], restricting further store loading. B, spark-dependent activation of Ca2+-activated Cl− channels causes spontaneous transient inward currents (STICs), with membrane depolarization and Ca2+ channel activation. This results in positive feedback, with Ca2+ release from the SR promoting further Ca2+ influx.