Role of elementary Ca2+ puffs in generating repetitive Ca2+ oscillations

Abstract

Inositol (1,4,5)-trisphosphate (IP 3 ) liberates intracellular Ca 2+ both as localized`puffs' and as repetitive waves that encode information in a frequency-dependent manner. Using video-rate confocal imaging, together with photorelease of IP 3 in Xenopus oocytes, we investigated the roles of puffs in determining the periodicity of global Ca 2+ waves. Wave frequency is not delimited solely by cyclical recovery of the cell's ability to support wave propagation, but further involves sensitization of Ca 2+ -induced Ca 2+ release by progressive increases in puff frequency and amplitude at numerous sites during the interwave period, and accumulation of pacemaker Ca 2+ , allowing a puff at à focal' site to trigger a subsequent wave. These speci®c focal' sites, distinguished by their higher sensitivity to IP 3 and close apposition to neighboring puff sites, preferentially entrain both the temporal frequency and spatial directionality of Ca 2+ waves. Although summation of activity from many stochastic puff sites promotes the generation of regularly periodic global Ca 2+ signals, the properties of individual Ca 2+ puffs control the kinetics of Ca 2+ spiking and the (higher) frequency of subcellular spikes in their local microdomain.

Frequency of elemental events of intracellularCa2+dynamics

“…In contrast to a constant Ca 2+ concentration, the nonlinear Fokker-Planck equation underestimates the results of the master equation. Nevertheless, the results in figure 7, which correspond to the stochastic fraction of the puff frequency, are in the same range as experimentally determined puff periods [8].…”

“…A puff is the spontaneous opening of channels of a single cluster. Experimental and theoretical studies have suggested that puffs play a pivotal role in intracellular Ca 2+ dynamics [8,11]. These investigations put forward the idea that all global patterns like Ca 2+ waves foot on Ca 2+ puffs.…”

“…Release is controlled by inositol-1,4,5-trisphosphate (IP 3 ) receptor channels (IP 3 R). They are arranged in clusters that comprise between 1 and 40 channels and that are randomly distributed on the membrane of the ER with distances between 1-7 µm [7,8]. IP 3 Rs have the important property that their open probability depends on the Ca 2+ concentration in the cytosol.…”

Linear noise approximation for stochastic oscillations of intracellular calcium

“…Similar conclusions apply to spatially extended systems [12][13][14][15]. As concerns calcium dynamics, stochasticity has been mainly associated to external disturbances [10,11].…”

Calcium wave pacemakers in eggs

“…1) Dumollard and Sardet, 2001). This 'pacemaker Ca 2+ rise' is a hallmark of low-frequency (period >20 seconds) Ca 2+ oscillations generated under constantly elevated Ins(1,4,5)P3 levels (Jacob, 1990;Marchant and Parker, 2001), which further suggests that a single and sustained Ins(1,4,5)P3 increase regulates the ascidian MI pacemaker and the mouse MII pacemaker.…”