Kostic, SandraPan, BinGuo, YuanYu, HongweiSapunar, DamirKwok, Wai-MengHudmon, AndyWu, Hsiang-EnHogan, Quinn H.2016-02-052016-02-052014-09Kostic, S., Pan, B., Guo, Y., Yu, H., Sapunar, D., Kwok, W.-M., … Hogan, Q. H. (2014). Regulation of Voltage-Gated Ca2+ Currents by Ca2+/Calmodulin-dependent Protein Kinase II in Resting Sensory Neurons. Molecular and Cellular Neurosciences, 62, 10–18. http://doi.org/10.1016/j.mcn.2014.07.0041044-7431https://hdl.handle.net/1805/8257Calcium/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 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.en-USPublisher PolicyCalciummetabolismCalcium-Calmodulin-Dependent Protein Kinase Type 2Ganglia, SpinalcytologySensory Receptor CellsArticle