Serine-1321-independent regulation of the μ1 adult skeletal muscle Na+ channel by protein kinase C

Saïd Bendahhou, Theodore R. Cummins, Jerald F. Potts, Jiefei Tong, William S. Agnew

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

The adult skeletal muscle Na+ channel μ1 possesses a highly conserved segment between subunit domains III and IV containing a consensus protein kinase C (PKC) phosphorylation site that, in the neuronal isoform, acts as a master control for 'convergent' regulation by PKC and cAMP-dependent protein kinase. It lacks an ≃200-aa segment between domains I and II thought to modulate channel gating. We here demonstrate that μ1 is regulated by PKC (but not cAMP-dependent protein kinase) in a manner distinct from that observed for the neuronal isoforms, suggesting that under the same conditions muscle excitation could be uncoupled from motor neuron input. Maximal phosphorylation by PKC, in the presence of phosphatase inhibitors, reduced peak Na+ currents by ≃90% by decreasing the maximal conductance, caused a - 15 mV shift in the midpoint of steady-state inactivation, and caused a slight speeding of inactivation. Surprisingly, these effects were not affected by mutation of the conserved serine (serine-1321) in the interdomain III-IV loop. The pattern of current suppression and gating modification by PKC resembles the response of muscle Na+ channels to inhibitory factors present in the serum and cerebrospinal fluid of patients with Guillain-Barre syndrome, multiple sclerosis, and idiopathic demyelinating polyradiculoneuritis.

Original languageEnglish (US)
Pages (from-to)12003-12007
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number26
DOIs
StatePublished - Dec 19 1995
Externally publishedYes

Keywords

  • Guillain-Barre syndrome
  • multiple sclerosis
  • neuromodulation

ASJC Scopus subject areas

  • General

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