Skeletal muscle fibres support store-operated Ca-entry (SOCE) across the t-tubular membrane upon exhaustive depletion of Ca from the sarcoplasmic reticulum (SR). Recently we demonstrated the presence of a novel mode of SOCE activated under conditions of maintained [Ca]. This phasic SOCE manifested in a fast and transient manner in synchrony with excitation contraction (EC)-coupling mediated SR Ca-release (Communications Biology 1:31， doi: https://doi.org/10.1038/s42003-018-0033-7). Stromal interaction molecule 1 (STIM1) and calcium release-activated calcium channel 1 (ORAI1)， positioned at the SR and t-system membranes， respectively， are the considered molecular correlate of SOCE. The evidence suggests ... More
Skeletal muscle fibres support store-operated Ca-entry (SOCE) across the t-tubular membrane upon exhaustive depletion of Ca from the sarcoplasmic reticulum (SR). Recently we demonstrated the presence of a novel mode of SOCE activated under conditions of maintained [Ca]. This phasic SOCE manifested in a fast and transient manner in synchrony with excitation contraction (EC)-coupling mediated SR Ca-release (Communications Biology 1:31， doi: https://doi.org/10.1038/s42003-018-0033-7). Stromal interaction molecule 1 (STIM1) and calcium release-activated calcium channel 1 (ORAI1)， positioned at the SR and t-system membranes， respectively， are the considered molecular correlate of SOCE. The evidence suggests that at the triads， where the terminal cisternae of the SR sandwich a t-tubule， STIM1 and ORAI1 proteins pre-position to allow for enhanced SOCE transduction. Here we show that phasic SOCE is not only shaped by global [Ca] but provide evidence for a local activation within nanodomains at the terminal cisternae of the SR. This feature may allow SOCE to modulate [Ca] during EC coupling. We define SOCE to occur on the same timescale as EC coupling and determine the temporal coherence of SOCE activation to SR Ca release. We derive a delay of 0.3 ms reflecting diffusive Ca-equilibration at the luminal ryanodine receptor 1 (RyR1) channel mouth upon SR Ca-release. Numerical simulations of Ca-calsequestrin binding estimates a characteristic diffusion length and confines an upper limit for the spatial distance between STIM1 and RyR1. Experimental evidence for a 4- fold change in t-system Ca-permeability upon prolonged electrical stimulation in conjunction with numerical simulations of Ca-STIM1 binding suggests a Ca dissociation constant of STIM1 below 0.35 mM. Our results show that phasic SOCE is intimately linked with RyR opening and closing， with only μs delays， because [Ca] in the terminal cisternae is just above the threshold for Ca dissociation from STIM1 under physiological resting conditions. This article is part of a Special Issue entitled: ECS Meeting edited by Claus Heizmann， Joachim Krebs and Jacques Haiech.
