title: Domain model for Ca2(+)-inactivation of Ca2+ channels at low channel density.
abstract: The "shell" model for Ca2(+)-inactivation of Ca2+ channels is based on the accumulation of Ca2+ in a macroscopic shell beneath the plasma membrane. The shell is filled by Ca2+ entering through open channels, with the elevated Ca2+ concentration inactivating both open and closed channels at a rate determined by how fast the shell is filled. In cells with low channel density, the high concentration Ca2+ "shell" degenerates into a collection of nonoverlapping "domains" localized near open channels. These domains form rapidly when channels open and disappear rapidly when channels close. We use this idea to develop a "domain" model for Ca2(+)-inactivation of Ca2+ channels. In this model the kinetics of formation of an inactivated state resulting from Ca2+ binding to open channels determines the inactivation rate, a mechanism identical with that which explains single-channel recordings on rabbit-mesenteric artery Ca2+ channels (Huang Y., J. M. Quayle, J. F. Worley, N. B. Standen, and M. T. Nelson. 1989. Biophys. J. 56:1023-1028). We show that the model correctly predicts five important features of the whole-cell Ca2(+)-inactivation for mouse pancreatic beta-cells (Plants, T. D. 1988. J. Physiol. 404:731-747) and that Ca2(+)-inactivation has only minor effects on the bursting electrical activity of these cells.
authors.affiliation: National Institutes of Health, National Institutes of Diabetes and Digestive and Kidney Diseases, Mathematical Research Branch, Bethesda, Maryland 20892.
authors.forename: A
authors.initials: A
authors.lastname: Sherman
authors.forename: J
authors.initials: J
authors.lastname: Keizer
authors.forename: J
authors.initials: J
authors.lastname: Rinzel
mesh_terms: D000818:Animals; D055592:Biophysical Phenomena; D001703:Biophysics; D002118:Calcium / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D004563:Electrochemistry; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D008954:Models, Biological
chemical_list: D015220:Calcium Channels; D002118:Calcium