Ja. Morrill et al., Gating of the L-type Ca channel in human skeletal myotubes: An activation defect caused by the hypokalemic periodic paralysis mutation R528H, J NEUROSC, 18(24), 1998, pp. 10320-10334
The skeletal muscle L-type Ca channel serves a dual role as a calcium-condu
cting pore and as the voltage sensor coupling t-tubule depolarization to ca
lcium release from the sarcoplasmic reticulum. Mutations in this channel ca
use hypokalemic periodic paralysis (HypoPP), a human autosomal dominant dis
order characterized by episodic failure of muscle excitability that occurs
in association with a decrease in serum potassium. The voltage-dependent ga
ting of L-type Ca channels was characterized by recording whole-cell Ca cur
rents in myotubes cultured from three normal individuals and from a patient
carrying the HypoPP mutation R528H. We found two effects of the R528H muta
tion on the L-type Ca current in HypoPP myotubes: (1) a mild reduction in c
urrent density and (2) a significant slowing of the rate of activation. We
also measured the voltage dependence of steady-state L-type Ca current inac
tivation and characterized, for the first time in a mammalian preparation,
the kinetics of both entry into and recovery from inactivation over a wide
range of voltages. The R528H mutation had no effect on the kinetics or volt
age dependence of inactivation.