Abstract
Store-operated calcium (Ca2+) entry (SOCE) in skeletal muscle is rapidly activated across the tubular system during direct activation of Ca2+ release. The tubular system is the invagination of the plasma membrane that forms junctions with the sarcoplasmic reticulum (SR) where STIM1, Orai1 and ryanodine receptors are found. The physiological activation of SOCE in muscle is not defined, thus clouding its physiological role. Here we show that the magnitude of a phasic tubular system Ca2+ influx is dependent on SR Ca2+ depletion magnitude, and define this as SOCE. Consistent with SOCE, the influx was resistant to nifedipine and BayK8644, and silenced by inhibition of SR Ca2+ release during excitation. The SOCE transient was shaped by action potential frequency and SR Ca2+ pump activity. Our results show that SOCE in skeletal muscle acts as an immediate counter-flux to Ca2+ loss across the tubular system during excitation-contraction coupling.
Highlights
Store-operated calcium (Ca2+) entry (SOCE) in skeletal muscle is rapidly activated across the tubular system during direct activation of Ca2+ release
SOCE has evolved to become a fast mechanism in skeletal muscle, probably in parallel with the evolution of the highly organised membrane structures that support the rapid transients of Ca2+ in the fibre evoked by action potentials[2]
The physiological activation mechanism and a primary physiological role of SOCE in skeletal muscle have not been defined, even though the molecular identities and biophysical properties of SOCE have been described in some detail[2,7,8,9]
Summary
The physiological activation mechanism and a primary physiological role of SOCE in skeletal muscle have not been defined, even though the molecular identities and biophysical properties of SOCE have been described in some detail[2,7,8,9]. Changing the Ca2+-buffering capacity of the cytoplasm allowed the manipulation of the ability of the tsystem to extrude Ca2+ during SR Ca2+ release[19,32] This exposed a role of rapidly activated SOCE during EC coupling was to act as an immediate counter-flux to t-system Ca2+ extrusion to prevent the loss of fibre Ca2+ during muscle stimulation. We suggest that SOCE is rapidly activated by local depletions of Ca2+ at the near membrane inside the SR terminal cisternae following the action potential-coordinated Ca2+ release. In the presence of a weakly Ca2+-buffered cytoplasmic environment, there was only a small net change in tlehveel[Coaf2+C]at-2sy+s-bduufrfienrginag train of action is equivalent potentials (Fig. 6) This to the situation in the muscle, so allowing a build-up of Ca2+ at the cytoplasmic side of the t-system membrane during EC coupling to cause activation of Ca2+ transport from the junctional space to the t-system lumen. SOCE captures Ca2+ that is extruded to the t-system and returns it to the cytoplasm before it would otherwise be lost to the external environment beyond the t-system lumen
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
