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• W2021105798 abstract "In skeletal muscle, there is bidirectional signalling between the L-type Ca2+ channel (1,4-dihydropyridine receptor; DHPR) and the type 1 ryanodine-sensitive Ca2+ release channel (RyR1) of the sarcoplasmic reticulum (SR). In the case of “orthograde signalling” (i.e., excitation-contraction coupling), the conformation of RyR1 is controlled by depolarization-induced conformational changes of the DHPR resulting in Ca2+ release from the SR. “Retrograde coupling” is manifested as enhanced L-type current. The nature of this retrograde signal, and its dependence on RyR1 conformation, are poorly understood. Here, we have examined L-type currents in normal myotubes after an exposure to ryanodine (200 μM, 1 h at 37°C) sufficient to lock RyR1 in a non-conducting, inactivated, conformational state. This treatment caused an increase in L-type current at less depolarized test potentials in comparison to myotubes similarly exposed to vehicle as a result of a ~5 mV hyperpolarizing shift in the voltage-dependence of activation. Charge movements of ryanodine-treated myotubes were also shifted to more hyperpolarizing potentials (~13 mV) relative to vehicle-treated myotubes. Enhancement of the L-type current by ryanodine was absent in dyspedic (RyR1 null) myotubes, indicating that ryanodine does not act directly on the DHPR. Our findings indicate that in retrograde signaling, the functional state of RyR1 influences conformational changes of the DHPR involved in activation of L-type current. This raises the possibility that physiological regulators of the conformational state of RyR1 (e.g., Ca2+, CaM, CaMK, redox potential) may also affect DHPR gating." @default.
• W2021105798 created "2016-06-24" @default.
• W2021105798 creator A5000882661 @default.
• W2021105798 creator A5057663126 @default.
• W2021105798 date "2009-09-01" @default.
• W2021105798 modified "2023-10-18" @default.
• W2021105798 title "Ryanodine modification of RyR1 retrogradely affects L-type Ca2+ channel gating in skeletal muscle" @default.
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• W2021105798 doi "https://doi.org/10.1007/s10974-009-9190-0" @default.
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