Regulation of voltage-gated Ca(2+) currents by Ca(2+)/calmodulin-dependent protein kinase II in resting sensory neurons. Mol Cell Neurosci 2014 Sep;62:10-8
Date
07/30/2014Pubmed ID
25064143Pubmed Central ID
PMC4187344DOI
10.1016/j.mcn.2014.07.004Scopus ID
2-s2.0-84906053798 (requires institutional sign-in at Scopus site) 9 CitationsAbstract
Calcium/calmodulin-dependent protein kinase II (CaMKII) is recognized as a key element in encoding depolarization activity of excitable cells into facilitated voltage-gated Ca(2+) channel (VGCC) function. Less is known about the participation of CaMKII in regulating VGCCs in resting cells. We examined constitutive CaMKII control of Ca(2+) 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.
Author List
Kostic S, Pan B, Guo Y, Yu H, Sapunar D, Kwok WM, Hudmon A, Wu HE, Hogan QHAuthors
Quinn H. Hogan MD Professor in the Anesthesiology department at Medical College of WisconsinWai-Meng Kwok PhD Professor in the Anesthesiology department at Medical College of Wisconsin
Hongwei Yu MD Professor in the Anesthesiology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsCalcium
Calcium Channel Blockers
Calcium Channels
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Ganglia, Spinal
Male
Membrane Potentials
Neurons, Afferent
Rats, Sprague-Dawley
Sensory Receptor Cells
