Factors affecting SOCE activation in mammalian skeletal muscle fibers

Abstract

Enzymatically dissociated mouse FDB muscle fibers, loaded with Fura-2 AM, were used to study the effect of mitochondrial uncoupling on the capacitative Ca(2+) entry, SOCE. Sarcoplasmic reticulum (SR) Ca(2+) stores were depleted by repetitive exposures to high K(+) or 4-chloro-m-Cresol (4-CmC) in the absence of extracellular Ca(2+). SR Ca(2+) store replenishment was substantially reduced using 5 microM cyclopiazonic acid (CPA). Readmission of external Ca(2+) (5 mM) increased basal [Ca(2+)](i) under two modalities. In mode 1 [Ca(2+)](i) initially increased at a rate of 0.8 +/- 0.1 nM/s and later at a rate of 12.3 +/- 2.6 nM/s, reaching a final value of 477.8 +/- 36.8 nM in 215.7 +/- 25.9 s. In mode 2, [Ca(2+)](i) increased at a rate of 0.8 +/- 0.1 nM/s to a value of 204.9 +/- 20.6 nM in 185.4 +/- 21.1 s. FCCP, 2 microM, reduced this Ca(2+) entry. In nine FCCP-poisoned fibers, the initial rate of Ca(2+) increase was 0.34 +/- 0.1 nM/s (mean +/- SEM), reaching a plateau of 149.2 +/- 14.1 nM in 217 +/- 19 s. The results may likely be explained by the hypothesis that SOCE is inhibited by mitochondrial uncouplers, pointing to a possible mitochondrial role in its activation. Using time-scan confocal microscopy and the dyes CaOr-5N AM or Rhod-2 AM to label mitochondrial Ca(2+), we show that during depletion [Ca(2+)](mito) initially increases and later diminishes. Finally, we show that the increase in basal [Ca(2+)](i), associated with SOCE activation, diminishes upon external Na(+) withdrawal. Na(+) entry through the SOCE pathway and activation of the reversal of Na(+)/Ca(2+) exchanger could explain this SOCE modulation by Na(+).

Toward the roles of store-operated Ca2+ entry in skeletal muscle

“…Thus, at the normal resting membrane potential, the store-dependent Ca 2+ influx is around 20 μM s −1 (relative to cytoplasmic volume [35]). This is consistent with the readdition of 2 mM of external Ca 2+ to the Ca 2+ -depleted intact fibres refilling the SR in 1 to 2 min [10,27,30], therefore accumulating ∼1 mM of Ca 2+ [25] in this period. It should be noted that the store-dependent Ca 2+ influx rate will slow with SOCE deactivation, which is dependent on SR refilling rate [14,22].…”

“…Following SOCE deactivation (when STIM1 is occupied by Ca 2+ , at low [Ca 2+ ] SR ), the SR Ca 2+ pump continues to load Ca 2+ into SR from the cytoplasm. Consistent with this is the low-amplitude transient increase in [Ca 2+ ] cyto due to store-dependent Ca 2+ entry into a Ca 2+ -depleted intact fibre in the absence of an SR Ca 2+ pump blocker and the continuous presence of 2-mM extracellular Ca 2+ [10,27].…”

Role of annexin A6 isoforms in catecholamine secretion by PC12 cells: Distinct influence on calcium response

“…Lack of ATP impairs plasma membrane potential (Na + /K + ‐ATPase is affected), having impact on NCX activity. Recent findings demonstrate that SOCE is inhibited by mitochondrial uncouplers [Bolanos et al, 2009]. Furthermore, it has been shown that SOC and NCX activities depend on each other.…”

“…Furthermore, it has been shown that SOC and NCX activities depend on each other. Na + entry through the SOCE pathway leads to activation of the reversal of Na + /Ca 2+ exchanger activity [Harper and Sage, 2007; Bolanos et al, 2009]. Moreover, NCX associates with F‐actin through its central hydrophilic domain [Conrdrescu and Reeves, 2006].…”

A focus on extracellular Ca2+ entry into skeletal muscle

“…It is surprising that SOCE even contributes to mitochondrial Ca 2+ movements in skeletal muscle. 72 , 176 In short, it seems that the role of extracellular Ca 2+ entry such as SOCE fine tunes every function of skeletal muscle.…”