title: Submicroscopic Ca2+ diffusion mediates inhibitory coupling between individual Ca2+ channels.
abstract: Dihydropyridine-sensitive Ca2+ channels in heart demonstrate an important negative feedback property: they close, or inactivate, in response to prior Ca2+ entry. We now find that Ca2+ influx through one channel can selectively contribute to the inactivation of another adjacent channel, without a generalized elevation of bulk intracellular Ca2+ concentration. Intracellular application of the Ca2+ chelator BAPTA greatly diminishes such negative interactions within Ca2+ channel pairs. These findings demonstrate that Ca2+ currents are controlled not only by intrinsic channel properties, but also by local diffusive interactions among neighboring channels. Such inhibitory coupling among channels provides a concrete example of localized Ca2+ signaling, long proposed to exist on the basis of theoretical calculations.
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: J P
authors.initials: JP
authors.lastname: Imredy
authors.forename: D T
authors.initials: DT
authors.lastname: Yue
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D002614:Chelating Agents / Q000494:pharmacology; D004058:Diffusion; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004553:Electric Conductivity; D005246:Feedback; D006168:Guinea Pigs; D015640:Ion Channel Gating / Q000502:physiology; D007700:Kinetics; D016276:Ventricular Function
chemical_list: D015220:Calcium Channels; D002614:Chelating Agents; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium