title: Integrative analysis of calcium signalling in cardiac muscle.
abstract: This review discusses the control of the amplitude of the cardiac systolic Ca transient. The Ca transient arises largely from release from the sarcoplasmic reticulum (SR). Release is triggered by calcium-induced calcium release (CICR) whereby the entry of a small amount of Ca on the L-type Ca current, "the trigger", results in the release of much more Ca from the SR. There are three potential control points: (1) the Ca content of the SR; (2) the properties of the SR Ca release channel or ryanodine receptor (RyR); (3) the amplitude of the L-type Ca current. The data reviewed show that the Ca content of the SR has pronounced effects on systolic [Ca2+]i and, reciprocally, the amount of Ca released from the SR affects sarcolemmal Ca fluxes thereby "autoregulating" SR content. Modulation of the ryanodine receptor has no steady-state effect due to compensating changes of SR Ca content. An increase of the L-type Ca current results in an abrupt increase of systolic [Ca2+]i with little change of SR content. This is because of a coordinated increase of both the trigger and loading function of the Ca current. These results emphasise the importance of considering all aspects of Ca handling in the context of SR Ca release and thus the regulation of the systolic Ca transient and contraction in cardiac muscle.
authors.affiliation: Unit of Cardiac Physiology, The University of Manchester, 1.524 Stopford Building, Oxford Rd, Manchester M13 9PT, UK.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Trafford
authors.forename: M E
authors.initials: ME
authors.lastname: Díaz
authors.forename: S C
authors.initials: SC
authors.lastname: O'Neill
authors.forename: D A
authors.initials: DA
authors.lastname: Eisner
mesh_terms: D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism; D020013:Calcium Signaling; D008954:Models, Biological; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
chemical_list: D020746:Calcium Channels, L-Type; D019837:Ryanodine Receptor Calcium Release Channel