Figure 3.

A proposed view of cardioprotection by effects of volatile anesthetics (VA) on mitochondrial Ca²⁺ overload. VA could mediate cardioprotection by mildly inhibiting mitochondrial NCE to increase [Ca²⁺]_m which triggers protective mechanisms before IR injury. Lowered ATP or higher Ca²⁺ -induced stimulation of mitochondrial K⁺ channels may lead to mild uncoupling by the K⁺-H⁺ exchanger (KHE) that may reduce ΔΨ_m and [Ca²⁺]_m during IR via the mitochondrial Ca²⁺ uniporter (CU) and/or the putative mitochondrial ryanodine receptor (mRyR). Lowered [Ca²⁺]_m would decrease “deleterious” ROS emission, impede mPTP opening, and reduce apoptotic/necrotic cell death on reperfusion. mPTP opening could also be prevented by a VA-mediated decrease in activation of glycogen synthase kinase (GSK-3β) via phosphorylation of GSK-3β. Effects of VA on channels/exchangers suggest potential implications for low Ca²⁺ and ROS in the triggering phase of VA cardioprotection.