Role in fast inactivation of conserved amino acids in the IV/S4-S5 loop of the human muscle Na+ channel

N. Mitrovic, H. Lerche, R. Heine, R. Fleischhauer, U. Pika-Hartlaub, U. Hartlaub, A. L. George, F. Lehmann-Horn*

*Corresponding author for this work

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Since it has been shown that point mutations in the S4-S5 loop of the Shaker K+ channel may disrupt fast inactivation, we investigated the role of three conserved amino acids in IV/S4-S5 of the adult human muscle Na+ channel (L1471, S1478, L1482). In contrast to the K+ channel mutations, the analogous substitutions in the Na+ channel (S1478A/C, L1482A) did not substantially affect fast inactivation. Nevertheless, the mutations S1478A/C/Q shifted the voltage dependence of steady-state inactivation; L1471Q and S1478C slowed recovery from inactivation. In contrast, a novel non-conserved IV/S4-S5 mutation causing paramyotonia congenita (F1473S) slowed fast inactivation 2-fold and accelerated recovery from inactivation 5-fold. The results indicate involvement of the IV/S4-S5 loop of the human muscle Na+ channel in fast inactivation, but different roles for conserved amino acids among Na+ and K+ channels.

Original languageEnglish (US)
Pages (from-to)9-12
Number of pages4
JournalNeuroscience Letters
Volume214
Issue number1
DOIs
StatePublished - Aug 16 1996

Keywords

  • Human
  • Inactivation
  • Myotonia
  • Na channel
  • Patch-clamp
  • Skeletal muscle

ASJC Scopus subject areas

  • Neuroscience(all)

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    Mitrovic, N., Lerche, H., Heine, R., Fleischhauer, R., Pika-Hartlaub, U., Hartlaub, U., George, A. L., & Lehmann-Horn, F. (1996). Role in fast inactivation of conserved amino acids in the IV/S4-S5 loop of the human muscle Na+ channel. Neuroscience Letters, 214(1), 9-12. https://doi.org/10.1016/S0304-3940(96)12866-4