Molecular basis for decreased muscle chloride conductance in the myotonic goat

Carol L. Beck, Christoph Fahlke, Alfred L. George*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

89 Scopus citations

Abstract

Certain forms of myotonia, a condition characterized by delayed relaxation of muscle secondary to sarcolemmal hyperexcitability, are caused by diminished chloride conductance in the muscle cell membrane. We have investigated the molecular basis for decreased muscle chloride conductance in the myotonic goat, an historically important animal model for the elucidation of the role of chloride in muscle excitation. A single nucleotide change causing the substitution of proline for a conserved alanine residue in the carboxyl terminus of the gnat muscle chloride channel (gCIC-l) was discovered. Heterologous expression of the mutation demonstrated a substantial (+47 mV) shift in the midpoint of steady-state activation of the channel, resulting in a diminished channel open probability at voltages near the resting membrane potential of skeletal muscle. These results provide a molecular basis for the decreased chloride conductance in myotonic muscle.

Original languageEnglish (US)
Pages (from-to)11248-11252
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number20
DOIs
StatePublished - Oct 1 1996

Keywords

  • action potential
  • chloride channel
  • electrophysiology
  • myotonia
  • skeletal muscle

ASJC Scopus subject areas

  • General

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