title: Analysis of cellular calcium fluxes in cardiac muscle to understand calcium homeostasis in the heart.
abstract: Central to controlling intracellular calcium concentration ([Ca(2+)](i)) are a number of Ca(2+) transporters and channels with the L-type Ca(2+) channel, Na(+)-Ca(2+) exchanger and sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) being of particular note in the heart. This review concentrates on the regulation of [Ca(2+)](i) in cardiac muscle and the homeostatic mechanisms employed to ensure that the heart can operate under steady-state conditions on a beat by beat basis. To this end we discuss the relative importance of various sources and sinks of Ca(2+) responsible for initiating contraction and relaxation in cardiac myocytes and how these can be manipulated to regulate the Ca(2+) content of the major Ca(2+) store, the sarcoplasmic reticulum (SR). We will present a simple feedback system detailing how such control can be achieved and highlight how small perturbations to the steady-state operation of the feedback loop can be both beneficial physiologically and underlie changes in systolic Ca(2+) in ageing and heart disease. In addition to manipulating the amplitude of the normal systolic Ca(2+) transient, the tight regulation of SR Ca(2+) content is also required to prevent the abnormal, spontaneous or diastolic release of Ca(2+) from the SR. Such diastolic events are a major factor contributing to the genesis of cardiac arrhythmias in disease situations and in recently identified familial mutations in the SR Ca(2+) release channel (ryanodine receptor, RyR). How such diastolic release arises and potential mechanisms for controlling this will be discussed.
authors.affiliation: Unit of Cardiac Physiology, University of Manchester, 3.08 Core Technology facility, 46 Grafton Street, Manchester M13 9PT, United Kingdom.
authors.forename: K M
authors.initials: KM
authors.lastname: Dibb
authors.forename: H K
authors.initials: HK
authors.lastname: Graham
authors.forename: L A
authors.initials: LA
authors.lastname: Venetucci
authors.forename: D A
authors.initials: DA
authors.lastname: Eisner
authors.forename: A W
authors.initials: AW
authors.lastname: Trafford
mesh_terms: D000375:Aging; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000502:physiology; D006331:Heart Diseases / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D017136:Ion Transport; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000502:physiology
chemical_list: D020746:Calcium Channels, L-Type; D019831:Sodium-Calcium Exchanger; D002118:Calcium