Abstract
Fast calcium transients (<10 ms) remain difficult to analyse in cellular microdomains, yet they can modulate key cellular events such as trafficking, local ATP production by endoplasmic reticulum-mitochondria complex (ER-mitochondria complex), or spontaneous activity in astrocytes. In dendritic spines receiving synaptic inputs, we show here that in the presence of a spine apparatus (SA), which is an extension of the smooth ER, a calcium-induced calcium release (CICR) is triggered at the base of the spine by the fastest calcium ions arriving at a Ryanodyne receptor (RyR). The mechanism relies on the asymmetric distributions of RyRs and sarco/ER calcium-ATPase (SERCA) pumps that we predict using a computational model and further confirm experimentally in culture and slice hippocampal neurons. The present mechanism for which the statistics of the fastest particles arriving at a small target, followed by an amplification, is likely to be generic in molecular transduction across cellular microcompartments, such as thin neuronal processes, astrocytes, endfeets, or protrusions.
Highlights
Extreme statistics describes the distribution of rare events, such as the first ions to find a small target [1, 2], which are difficult to detect experimentally in biological microdomains
Fast calcium transient in spines with and without a spine apparatus (SA) are not due to classical diffusion To investigate the role of the SA, we first released calcium following the flashes of ND-YAG UV laser to uncage calcium in dendritic spines from hippocampal neurons (Fig 1A)
We conclude that fast calcium transients at the base of the SP+ spines did not depend on the mode of induction, as they could be induced by calcium and glutamate uncaging with similar time scale
Summary
Extreme statistics describes the distribution of rare events, such as the first ions to find a small target [1, 2], which are difficult to detect experimentally in biological microdomains. We use stochastic simulations to show that after calcium release in the spine head, under the hypothesis that RyRs are located at the base and SERCA in the head of spine, the fastest ions arriving at the base determine the time scale of calcium transients due to an amplification step. We further confirm this hypothesis experimentally using imaging in culture and slice hippocampal neuron. This mechanism is likely to define the time scale of biochemical activation in nano- and microdomains, when the source of diffusing particles and the binding targets are spatially separated
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