Ryanodine Receptor Adaptation: Control Mechanism of Ca 2+ -Induced Ca 2+ Release in Heart

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Abstract
Adaptation of single cardiac ryanodine receptor (RyR) channels was demonstrated by application of the caged calcium ion (Ca2+) methodology. In contrast to conventional desensitization found in surface membrane ligand-gated channels, single cardiac RyR channels adapted to maintained Ca2+ stimuli, preserving their ability to respond to a second (larger) Ca2+ stimulus. RyR adaptation may represent a molecular control mechanism for smoothly graded Ca(2+)-induced Ca2+ release in heart and may be a fundamental feature of channels, including the inositol triphosphate receptor, that are involved in intracellular Ca2+ signaling in many cell types.