Mitochondrial permeability transition pore and calcium handling

The opening of a large conductance channel in the inner mitochondrial membrane, known as the mitochondrial permeability transition pore (PTP), has been shown to be a primary mediator of cell death in the heart subjected to ischemia-reperfusion injury. Inhibitors of the PTP have been shown to reduce cardiac ischemia-reperfusion injury in many animal models. Furthermore, most cardioprotective strategies appear to reduce ischemic cell death either by reducing the triggers for the opening of the PTP, such as reducing calcium overload or reactive oxygen species, or by inhibiting PTP modulators. This chapter will focus on key issues in the study of the PTP and provide some methods for measuring PTP opening in isolated mitochondria.