Channel adaptation is a fundamental feature of sarcoplasmic reticulum calcium release channels (called ryanodine receptors, RyRs). It permits successive increases in the intracellular concentration of calcium (Ca²⁺) to repeatedly but transiently activate channels. Adaptation of RyRs in the absence of magnesium (Mg2+) and adenosine triphosphate is an extremely slow process (taking seconds). Photorelease of Ca²⁺ from nitrophenyl-EGTA, a photolabile Ca²⁺ chelator, demonstrated that RyR adaptation is rapid (milliseconds) in canine heart muscle when physiological Mg²⁺ concentrations are present. Phosphorylation of the RyR by protein kinase A increased the responsiveness of the channel to Ca²⁺ and accelerated the kinetics of adaptation. These properties of the RyR from heart may also be relevant to other cells in which multiple agonist-dependent triggering events regulate cellular functions.