On the Loose: Uncaging Ca²⁺-induced Ca²⁺ Release in Smooth Muscle

Movement of Ca²⁺ from intracellular stores into the cytosol is an essential component of excitation–contraction coupling in muscle. In cardiac and smooth muscle, Ca²⁺ is released from the sarcoplasmic reticulum (SR) in response to Ca²⁺ influx by a process of Ca²⁺-induced Ca²⁺ release (CICR). First described by Lederer and coworkers in cardiac myocytes (Cheng et al., 1993), highly localized cytosolic Ca²⁺ transients, called Ca²⁺ sparks, originating from ryanodine-sensitive Ca²⁺-release channels (ryanodine receptors [RyRs]) in the SR membrane, are thought to be the elementary intracellular Ca²⁺ release events in excitation–contraction coupling, not only in cardiac muscle but also in skeletal (Klein et al., 1996) and smooth muscle (Nelson et al., 1995). RyRs are formed by a family of intracellular Ca²⁺ channel subunits (RyR1–3), which span the SR membrane...