KCNMA1 and Cowden syndrome 1: A second limitation is that although paxilline is regarded as a specific BK channel blocker, it also can inhibit Ca2+ uptake by sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) at concentrations ≥5 μM, thereby potentially modifying intracellular Ca2+ signaling, a pathway already disrupted in IR injury as well as CS injury [77,78,79,80].