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Stochastic simulation of a single inositol 1,4,5-trisphosphate-sensitive Ca2+ channel reveals repetitive openings during 'blip-like' Ca2+ transients

par Swillens, Stéphane ;Champeil, Philippe;Combettes, Laurent;Dupont, Geneviève
Référence Cell calcium, 23, page (291-302)
Publication Publié, 1998

Article révisé par les pairs

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Résumé :

Confocal microscope studies with fluorescent dyes of inositol 1,4,5-trisphosphate (InsP,)-induced intracellular Ca*+ mobilization recently established the existence of ‘elementary’ events, dependent on the activity of individual InsP,-sensitive Ca2+ channels. In the present work, we try by theoretical stochastic simulation to explain the smallest signals observed in those studies, which were referred to as Ca 2+ ‘blips’ [Parker I., Yao Y. Ca*+ transients associated with openings of inositol trisphosphate-gated channels in Xenopus oocytes. J Physiol Land 1996; 491: 663-6681. For this purpose, we assumed a simple molecular model for the InsP,-sensitive Ca*+ channel and defined a set of parameter values accounting for the results obtained in electrophysiological bilayer experiments [Bezprozvanny I., Watras J., Ehrlich B.E. Bell-shaped calcium-response curves of lns(1,4,5)P,- and calcium- gated channels from endoplasmic reticulum of cerebellum. Nature 1991; 351: 751-754; Bezprozvanny I., Ehrlich B.E. lnositol (1,4,5)-trisphosphate (InsP,)-gated Ca channels from cerebellum: conduction properties for divalent cations and regulation by intraluminal calcium. J Gen Physiol1994; 104: 821-8561. With a stochastic procedure which considered cytosolic Ca*+ diffusion explicitly, we then simulated the behaviour of a single channel, placed in a realistic physiological environment. An attractive result was that the simulated channel exhibited bursts of activity, arising from repetitive channel openings, which were responsible for transient rises in Ca*+ concentration and were reminiscent of the relatively long-duration experimental Ca2+ blips. The influence of the values chosen for the various parameters (affinity and diffusion coefficient of the buffers, luminal Ca*+ concentration) on the kinetic characteristics of these theoretical blips is analyzed.