Bidirectional control of BK channel open probability by CAMKII and PKC in medial vestibular nucleus neurons

Ingrid van Welie, Sascha du Lac

Research output: Contribution to journalArticlepeer-review

Abstract

Large conductance K+ (BK) channels are a key determinant of neuronal excitability. Medial vestibular nucleus (MVN) neurons regulate eye movements to ensure image stabilization during head movement, and changes in their intrinsic excitability may play a critical role in plasticity of the vestibulo-ocular reflex. Plasticity of intrinsic excitability in MVN neurons is mediated by kinases, and BK channels influence excitability, but whether endogenous BK channels are directly modulated by kinases is unknown. Double somatic patch-clamp recordings from MVN neurons revealed large conductance potassium channel openings during spontaneous action potential firing. These channels displayed Ca2+ and voltage dependence in excised patches, identifying Mthem as BK channels. Recording isolated single channel currents at physiological temperature revealed a novel kinase-mediated bidirectional control in the range of voltages over which BK channels are activated. Application of activated Ca2 /calmodulin-dependent kinase II (CAMKII) increased BK channel open probability by shifting the voltage activation range towards more hyperpolarized potentials. An opposite shift in BK channel open probability was revealed by inhibition of phosphatases and was occluded by blockade of protein kinase C (PKC), suggesting that active PKC associated with BK channel complexes in patches was responsible for this effect. Accordingly, direct activation of endogenous PKC by PMA induced a decrease in BK open probability. BK channel activity affects excitability in MVN neurons and bidirectional control of BK channels by CAMKII, and PKC suggests that cellular signaling cascades engaged during plasticity may dynamically control excitability by regulating BK channel open probability.

Original languageEnglish (US)
Pages (from-to)1651-1659
Number of pages9
JournalJournal of neurophysiology
Volume105
Issue number4
DOIs
StatePublished - Apr 2011
Externally publishedYes

Keywords

  • Calmodulin-dependent kinase ii
  • Firing rate potentiation
  • Large conductance potassium channels
  • Phosphorylation
  • Protein kinase c
  • Ves-tibular nucleus
  • Vestibulo-ocular reflex

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

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