SK channels are necessary but not sufficient for denervation-induced hyperexcitability

David Jacobson, Paco S. Herson, Torben R. Neelands, James Maylie, John P. Adelman

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Skeletal muscle hyperexcitability is characteristically associated with denervation. Expression of SK3, a small conductance Ca2+-activated K+ channel (SK channel) in skeletal muscle is induced by denervation, and direct application of apamin, a peptide blocker of SK channels, dramatically reduces hyperexcitability. To investigate the role of SK3 channels in denervation-induced hyperexcitability, SK3 expression was manipulated using a transgenic mouse that harbors a tetracycline-regulated SK3 gene. Electromyographic (EMG) recordings from anterior tibial (AT) muscle showed that denervated muscle from transgenic or wild-type animals had equivalent hyperexcitability that was blocked by apamin. In contrast, denervated skeletal muscle from SK3tTA mice lacking SK3 channels showed little or no hyperexcitability, similar to results from wild-type innervated skeletal muscle. However, innervated skeletal muscle from SK3tTA mice containing SK3 channels did not show hyperexcitability. The results demonstrate that SK3 channels are necessary but not sufficient for denervation-induced skeletal muscle hyperexcitability.

Original languageEnglish (US)
Pages (from-to)817-822
Number of pages6
JournalMuscle and Nerve
Volume26
Issue number6
DOIs
StatePublished - Dec 1 2002

Keywords

  • Denervation
  • Electromyography
  • Hyperexcitability
  • SK3
  • Skeletal muscle

ASJC Scopus subject areas

  • Physiology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Physiology (medical)

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