Role of the cytoskeleton in communication between L-type Ca2+channels and mitochondria

Abstract

The L-type Ca(2+) channel is the main route for Ca(2+) entry into cardiac myocytes, which is essential for the maintenance of cardiac excitation and contraction. Alterations in L-type Ca(2+) channel activity and Ca(2+) homeostasis have been implicated in the development of cardiomyopathies. Cardiac excitation and contraction is fuelled by ATP, synthesized predominantly by the mitochondria via the Ca(2+)-dependent process oxidative phosphorylation. Mitochondrial reactive oxygen species (ROS) are by-products of oxidative phosphorylation and are associated with the development of cardiac pathology. The cytoskeleton plays a role in the communication of signals from the plasma membrane to intracellular organelles. There is good evidence that both L-type Ca(2+) channel activity and mitochondrial function can be modulated by changes in the cytoskeletal network. Activation of the L-type Ca(2+) channel can regulate mitochondrial function through cytoskeletal proteins as a result of transmission of movement from the β(2)-subunit of the channel that occurs during activation and inactivation of the channel. An association between cytoskeletal proteins and the mitochondrial voltage-dependent anion channel (VDAC) may play a role in this response. The L-type Ca(2+) channel is the initiator of contraction in cardiac muscle and the VDAC is responsible for regulating mitochondrial ATP/ADP trafficking. This article presents evidence that a functional coupling between L-type Ca(2+) channels and mitochondria may assist in meeting myocardial energy demand on a beat-to-beat basis.