Absence of Ca2+ current facilitation in skeletal muscle of transgenic mice lacking the type 1 ryanodine receptor.

AUTOR(ES)

Fleig, A

RESUMO

1. Whole-cell patch-clamp recordings were used to study voltage-dependent facilitation of Ca2+ currents and excessive Ca2+ tail current in skeletal myoballs cultured from wild-type and transgenic mice expressing a null mutation of the ryanodine receptor (RyR) type 1 (dyspedic myoballs). 2. Ca2+ current density in dyspedic myoballs was reduced by about 60% compared with wild-type cells, with dihydropyridine-binding capacity largely retained. 3. Strong and long-lasting depolarizations (+80 mV and 600 ms), which normally produce excessive tail currents upon repolarization in control cells, failed to do so in dyspedic myoballs. 4. Dyspedic myoballs also failed to produce both Ca2+ current facilitation and the left shift of the current-voltage (I-V) curve induced by paired-pulse stimulation. 5. We propose that excessive tail currents and facilitation arise from silent Ca2+ channels acting as the voltage sensors in excitation-contraction coupling.

Documentos Relacionados

• Ca(2+)-induced Ca2+ release in myocytes from dyspedic mice lacking the type-1 ryanodine receptor.
• Reduced Ca2+ current, charge movement, and absence of Ca2+ transients in skeletal muscle deficient in dihydropyridine receptor beta 1 subunit.
• Single-channel properties of the recombinant skeletal muscle Ca2+ release channel (ryanodine receptor).
• Calmodulin activation and inhibition of skeletal muscle Ca2+ release channel (ryanodine receptor).
• Modulation of L-type Ca2+ current but not activation of Ca2+ release by the gamma1 subunit of the dihydropyridine receptor of skeletal muscle