Regulation of voltage-gated Ca2+ currents by Ca2+/calmodulin-dependent protein kinase II in resting sensory neurons

Sandra Kostic, Bin Pan, Yuan Guo, Hongwei Yu, Damir Sapunar, Wai Meng Kwok, Andy Hudmon, Hsiang En Wu, Quinn H. Hogan

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Calcium/calmodulin-dependent protein kinase II (CaMKII) is recognized as a key element in encoding depolarization activity of excitable cells into facilitated voltage-gated Ca2+ channel (VGCC) function. Less is known about the participation of CaMKII in regulating VGCCs in resting cells. We examined constitutive CaMKII control of Ca2+ currents in peripheral sensory neurons acutely isolated from dorsal root ganglia (DRGs) of adult rats. The small molecule CaMKII inhibitor KN-93 (1.0μM) reduced depolarization-induced ICa by 16-30% in excess of the effects produced by the inactive homolog KN-92. The specificity of CaMKII inhibition on VGCC function was shown by the efficacy of the selective CaMKII blocking peptide autocamtide-2-related inhibitory peptide in a membrane-permeable myristoylated form, which also reduced VGCC current in resting neurons. Loss of VGCC currents is primarily due to reduced N-type current, as application of mAIP selectively reduced N-type current by approximately 30%, and prior N-type current inhibition eliminated the effect of mAIP on VGCCs, while prior block of L-type channels did not reduce the effect of mAIP on total ICa. T-type currents were not affected by mAIP in resting DRG neurons. Transduction of sensory neurons in vivo by DRG injection of an adeno-associated virus expressing AIP also resulted in a loss of N-type currents. Together, these findings reveal a novel molecular adaptation whereby sensory neurons retain CaMKII support of VGCCs despite remaining quiescent.

Original languageEnglish (US)
Pages (from-to)10-18
Number of pages9
JournalMolecular and Cellular Neuroscience
Volume62
DOIs
StatePublished - Sep 2014

Keywords

  • Calcium signaling
  • Calcium/calmodulin-dependent protein kinase II
  • Sensory neuron
  • Voltage-gated calcium channel

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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