Coupled gating of skeletal muscle ryanodine receptors is modulated by Ca2+, Mg2+, and ATP.
Coupled gating of skeletal muscle ryanodine receptors is modulated by Ca2+, Mg2+, and ATP.
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骨骼肌兰尼碱受体的耦合门控由 Ca2、Mg2 和 ATP 调节。
DOI：
10.1152/ajpcell.00150.2012
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Copello,JulioA
中科院分区：
文献类型：
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作者：
Porta,Maura;Diaz-Sylvester,PaulaL;Neumann,JakeT;Escobar,ArielL;Fleischer,Sidney;Copello,JulioA
Coupled gating (synchronous openings and closures) of groups of skeletal muscle ryanodine receptors (RyR1), which mimics RyR1-mediated Ca2+release underlying Ca2+sparks, was first described by Marx et al. (Marx SO, Ondrias K, Marks AR.Science281: 818–821, 1998). The nature of the RyR1-RyR1 interactions for coupled gating still needs to be characterized. Consequently, we defined planar lipid bilayer conditions where ∼25% of multichannel reconstitutions contain mixtures of coupled and independently gating RyR1. In ∼10% of the cases, all RyRs (2–10 channels; most frequently 3–4) gated in coupled fashion, allowing for quantification. Our results indicated that coupling required cytosolic solutions containing ATP/Mg2+and high (50 mM) luminal Ca2+(Calum) or Sr2+solutions. Bursts of coupled activity (events) started and ended abruptly, with all channels activating/deactivating within ∼300 μs. Coupled RyR1 were heterogeneous, where highly active RyR1 (“drivers”) seemed open during the entire coupled event (Po= 1), while other RyR1s (“followers”) displayed abundant flickering and smaller amplitude. Drivers mean open time increased with cytosolic Ca2+(Cacyt) or caffeine, whereas followers flicker frequency was Cacytindependent and more sensitive to inhibition by cytosolic Mg2+. Coupled events were insensitive to varying lumen-to-cytosol Ca2+fluxes from ∼1 to 8 pA, which does not corroborate coupling of neighboring RyR1 by local Ca2+-induced Ca2+release. However, coupling requires specific Calumsites, as it was lost when Calumwas replaced by luminal Ba2+or Mg2+. In summary, coupled events reveal complex interactions among heterogeneous RyR1, differentially modulated by cytosolic ATP/Mg2+, Cacyt, and Calum,which under cell-like ionic conditions may parallel synchronous RyR1 gating during Ca2+sparks.
