Pharmacological Regulators of Intracellular Calcium Release Channels

Intracellular Ca2+ release channels, such as inositol 1,4,5-trisphosphate receptors (IP3Rs) and ryanodine receptors (RyRs), facilitate the release of Ca2+ from intracellular storage organelles in response to extracellular and intracellular stimuli. Consequently, these large, tetrameric proteins play a central role in Ca2+ signalling and Ca2+ homeostasis in virtually all cells. Recent data suggests that intracellular Ca2+ release channels may also have an important pathophysiological function in certain disease states, including cardiac arrhythmias and heart failure. As a result, there has been much interest in the identification and characterization of novel, selective regulators of these channels. In this article, we review the wide array of pharmacological agents that interact directly with intracellular Ca2+ release channels and describe the mechanisms underlying their ability to modify channel function.