title: Role of the cytoskeleton in communication between L-type Ca(2+) 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.
authors.affiliation: Cardiovascular Electrophysiology Laboratory, School of Anatomy, Physiology and Human Biology, The University of Western Australia, Crawley, WA, Australia.
authors.forename: Helena M
authors.initials: HM
authors.lastname: Viola
authors.forename: Livia C
authors.initials: LC
authors.lastname: Hool
mesh_terms: D002118:Calcium / Q000502:physiology; D020746:Calcium Channels, L-Type / Q000737:chemistry / Q000378:metabolism*; D009202:Cardiomyopathies / Q000378:metabolism / Q000473:pathology; D003599:Cytoskeleton / Q000473:pathology / Q000502:physiology*; D006321:Heart / Q000502:physiology; D006331:Heart Diseases / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008929:Mitochondria, Heart / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure
chemical_list: D020746:Calcium Channels, L-Type; D002118:Calcium