Ca2+ store determines gating of store operated calcium entry in mammalian skeletal muscle.
This work describes the gating of the store operated calcium entry (SOCE) in adult mammalian skeletal muscle. Flexor digitorum brevis fibers (FDB) were isolated from adult mice and exposed to conditions to deplete the sarcoplasmic reticulum (SR). A transient SR depletion caused either by repetitive depolarizations, chlorocresol (CMC) or, cyclopiazonic acid (CPA) induced a bell shaped calcium entry that raised the [Ca(2+)](i) to a maximum of 27.09 +/- 4.35 nM from the resting value. The activation time to reach 10-90% of the maximum amplitude was 112 +/- 10 s (n = 22). On the other hand, any mechanism that caused a permanent SR depletion (like thapsigargin, continuous CPA, or continuous CMC) triggered a calcium entry pathway that lasted 325 +/- 23 s and raised the [Ca(2+)](i )to 129.50 +/- 13.05 nM from the resting level (n = 28). Then, a prolonged depletion triggered an increase in [Ca(2+)](i) to higher values and for a longer time than when the SR is transiently depleted (p < 0.001). Our results, in skeletal muscle, showed that calcium store depletion was the signal for SOCE activation and how the SR got depleted was not relevant. Also, we found that SOCE deactivation was not caused by [Ca(2+)](i) but by the SR content. Our results suggest that the SR calcium content plays an important role in SOCE gating in mammalian skeletal muscle and a calcium sensor is located inside the SR.
González Narváez
Adom A
AA
Laboratorio de Cardiología Molecular, Centro de Biociencia, Fundación Instituto de Estudios Avanzados, Car. Nac. Hoyo de Puerta, Sartenejas, Baruta, Caracas 1080, Venezuela. agonzalez@idea.gob.ve
Castillo
A
A
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002478:Cells, Cultured; D003408:Cresols / Q000494:pharmacology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D003408:Cresols; D004791:Enzyme Inhibitors; D007211:Indoles; D019837:Ryanodine Receptor Calcium Release Channel; C006984:chlorocresol; D002118:Calcium; C000543:cyclopiazonic acid