Role of the cytoskeleton in communication between L ‐type C a 2+ channels and mitochondria

Summary The L ‐type C a 2+ channel is the main route for C a 2+ entry into cardiac myocytes, which is essential for the maintenance of cardiac excitation and contraction. Alterations in L ‐type C a 2+ channel activity and C a 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 C a 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 C a 2+ channel activity and mitochondrial function can be modulated by changes in the cytoskeletal network. Activation of the L ‐type C a 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 C a 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 C a 2+ channels and mitochondria may assist in meeting myocardial energy demand on a beat‐to‐beat basis.