title: Calcium signalling in cardiac muscle: refractoriness revealed by coherent activation.
abstract: Contraction of cardiac myocytes is governed by calcium-ion (Ca2+ )-induced Ca2+ release (CICR) from the sarcoplasmic reticulum through Ca2+-release channels. Ca2+ release occurs by concerted activation of numerous elementary Ca2+ events, 'Ca2+ sparks', that are triggered and locally controlled by Ca2+ influx into the cell through plasmalemmal L-type Ca2+ channels. Because of the positive feedback inherent in CICR, an as-yet-unidentified control mechanism is required to restrain the amplification of Ca2+ signalling and to terminate Ca2+ release from the sarcoplasmic reticulum. Here we use ultraviolet-laser-flash and two-photon photolysis of caged Ca2+ to study spatiotemporal features of the termination and refractoriness of Ca2+ release. Coherent and simultaneous activation of all Ca2+-release sites within a cardiac myocyte unmasked a prominent refractoriness, recovering monotonically within about 1 second. In contrast, selective activation of a few Ca 2+-release sites was not followed by a refractoriness of Ca 2+ release from the sarcoplasmic reticulum. This discrepancy is consistent with the idea that a functional depletion of Ca2+ from the cellular sarcoplasmic-reticulum network may underlie the refractoriness of CICR observed after a whole-cell Ca2+ transient. These results also imply the requirement for further mechanisms to terminate spatially limited subcellular Ca2+-release events such as Ca2+ sparks.
authors.affiliation: Department of Physiology, University of Bern, Bühlplatz 5, 3012 Bern, Switzerland.
authors.forename: F
authors.initials: F
authors.lastname: DelPrincipe
authors.forename: M
authors.initials: M
authors.lastname: Egger
authors.forename: E
authors.initials: E
authors.lastname: Niggli
mesh_terms: D000818:Animals; D020013:Calcium Signaling; D004594:Electrophysiology; D006168:Guinea Pigs; D009206:Myocardium / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism / Q000502:physiology; D019831:Sodium-Calcium Exchanger / Q000502:physiology
chemical_list: D019831:Sodium-Calcium Exchanger