title: Mechanisms responsible for quantal Ca2+ release from inositol trisphosphate-sensitive calcium stores.
abstract: Activation of cells by hormones, growth factors or neurotransmitters leads to an increased production of inositol trisphosphate (InsP3) and, after activation of the InsP3 receptor (InsP3R), to Ca2+ release from intracellular Ca2+ stores. The release of intracellular Ca2+ is characterised by a graded response when submaximal doses of agonists are used. The basic phenomenon, called "quantal Ca2+ release", is that even the maintained presence of a submaximal dose of agonist or of InsP3 for long time periods (up to 20 min) provokes only a partial release of Ca2+. This partial, or quantal, release phenomenon is due to the fact that the initially very rapid InsP3-induced Ca2+ release eventually develops into a much slower release phase. Physiologically, quantal release allows the Ca2+ stores to function as increment detectors and to induce local Ca2+ responses. The basic mechanism for quantal release of Ca2+ is presently not known. Possible mechanisms to explain the quantal behaviour of InsP3- induced Ca2+ release include the presence of InsP3Rs with varying sensitivities for InsP3, heterogeneous InsP3R distribution, intrinsic inactivation of the InsP3Rs, and regulation of the InsP3Rs by Ca2+ store content. This article reviews critically the evidence for the various mechanisms and evaluates their functional importance. A Ca2+-mediated conformational change of the InsP3R is most likely the key feature of the mechanism for quantal Ca2+ release, but the exact mode of operation remains unclear. It should also be pointed out that in intact cells more than one mechanism can be involved.
authors.affiliation: Laboratorium voor Fysiologie, Campus Gasthuisberg O/N-K.U.Leuven, B-3000 Leuven, Belgium.
authors.forename: J B
authors.initials: JB
authors.lastname: Parys
authors.forename: L
authors.initials: L
authors.lastname: Missiaen
authors.forename: H D
authors.initials: HD
authors.lastname: Smedt
authors.forename: I
authors.initials: I
authors.lastname: Sienaert
authors.forename: R
authors.initials: R
authors.lastname: Casteels
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007293:Inosine Triphosphate / Q000494:pharmacology*
chemical_list: D007293:Inosine Triphosphate; D002118:Calcium