STOCHASTIC SIMULATION OF A SINGLE INOSITOL 1,4,5-TRISPHOSPHATE-SENSITIVE CA2-LIKE CA2+ TRANSIENTS( CHANNEL REVEALS REPETITIVE OPENINGS DURING BLIP)

Confocal microscope studies with fluorescent dyes of inositol 1,4,5-tr isphosphate (InsP(3))-induced intracellular Ca2+ mobilization recently established the existence of 'elementary' events, dependent on the ac tivity of individual InsP(3)-sensitive Ca2+ channels. In the present w ork, we try by theoretical stochastic simulation to explain the smalle st signals observed in those studies, which were referred to as Ca2+ ' blips' [Parker I., Yao Y. Ca2+ transients associated with openings of inositol trisphosphate-gated channels in Xenopus oocytes. J Physiol Le nd 1996; 491. 663-668]. For this purpose, we assumed a simple molecula r model for the InsP(3)-sensitive Ca(2+ )channel and defined a set of parameter values accounting for the results obtained in electrophysiol ogical bilayer experiments [Bezprozvanny I., Watras J., Ehrlich B.E. B ell-shaped calcium-response curves of Ins(1,4,5)P-3- and calcium-gated channels from endoplasmic reticulum of cerebellum. Nature 1991; 351. 751-754; Bezprozvanny I., Ehrlich B.E. Inositol (1,4,5)trisphosphate ( InsP(3))-gated Ca channels from cerebellum: conduction properties for divalent cations and regulation by intraluminal calcium, J Gen Physiol 1994; 104. 821-856]. With a stochastic procedure which considered cyt osolic Ca2+ diffusion explicitly, we then simulated the behaviour of a single channel, placed in a realistic physiological environment. An a ttractive result was that the simulated channel exhibited bursts of ac tivity, arising from repetitive channel openings, which were responsib le for transient rises in Ca2+ concentration and were reminiscent of t he relatively long-duration experimental Ca2+ blips. The influence of the values chosen for the various parameters (affinity and diffusion c oefficient of the buffers, luminal Ca2+ concentration) on the kinetic characteristics of these theoretical blips is analyzed.