Gating of the L-type Ca channel in human skeletal myotubes: An activation defect caused by the hypokalemic periodic paralysis mutation R528H

James A. Morrill, Robert H. Brown, Stephen C. Cannon

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The skeletal muscle L-type Ca channel serves a dual role as a calcium- conducting pore and as the voltage sensor coupling t-tubule depolarization to calcium release from the sarcoplasmic reticulum. Mutations in this channel cause hypokalemic periodic paralysis (HypoPP), a human autosomal dominant disorder characterized by episodic failure of muscle excitability that occurs in association with a decrease in serum potassium. The voltage-dependent gating of L-type Ca channels was characterized by recording whole-cell Ca currents in myotubes cultured from three normal individuals and from a patient carrying the HypoPP mutation R528H. We found two effects of the R528H mutation on the L-type Ca current in HypoPP myotubes: (1) a mild reduction in current density and (2) a significant slowing of the rate of activation. We also measured the voltage dependence of steady-state L-type Ca current inactivation 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 voltage dependence of inactivation.

Original languageEnglish (US)
Pages (from-to)10320-10334
Number of pages15
JournalJournal of Neuroscience
Issue number24
StatePublished - Dec 15 1998



  • Cultured cells
  • Dihydropyridine receptor
  • Familial periodic paralysis
  • Human skeletal muscle
  • L-type calcium channel
  • Patch clamp

ASJC Scopus subject areas

  • Neuroscience(all)

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