title: Regulation of voltage-gated Ca(2+) currents by Ca(2+)/calmodulin-dependent protein kinase II in resting sensory neurons.
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 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.
authors: Medical College of Wisconsin, Department of Anesthesiology, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. Electronic address: sandra.kostic@mefst.hr.
authors: Sandra
authors: S
authors: Kostic
authors: Medical College of Wisconsin, Department of Anesthesiology, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. Electronic address: bpan@mcw.edu.
authors: Bin
authors: B
authors: Pan
authors: Medical College of Wisconsin, Department of Anesthesiology, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. Electronic address: guoy@mcw.edu.
authors: Yuan
authors: Y
authors: Guo
authors: Medical College of Wisconsin, Department of Anesthesiology, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. Electronic address: hyu@mcw.edu.
authors: Hongwei
authors: H
authors: Yu
authors: Department of Anatomy, Histology and Embryology, University of Split School of Medicine, Split, Croatia. Electronic address: damir.sapunar@mefst.hr.
authors: Damir
authors: D
authors: Sapunar
authors: Medical College of Wisconsin, Department of Anesthesiology, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. Electronic address: wmkwok@mcw.edu.
authors: Wai-Meng
authors: WM
authors: Kwok
authors: Indiana University School of Medicine, Department of Biochemistry and Molecular Biology, Stark Neuroscience Research Institute, 950 West Walnut (R2-480), Indianapolis, IN 46202, USA. Electronic address: ahudmon@iu.edu.
authors: Andy
authors: A
authors: Hudmon
authors: Medical College of Wisconsin, Department of Anesthesiology, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. Electronic address: hwu@mcw.edu.
authors: Hsiang-En
authors: HE
authors: Wu
authors: Medical College of Wisconsin, Department of Anesthesiology, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA; Zablocki VA Medical Center, 5000W. National Avenue, Milwaukee, WI 53295, USA. Electronic address: qhogan@mcw.edu.
authors: Quinn H
authors: QH
authors: Hogan
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000166:cytology*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009475:Neurons, Afferent / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism*
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002118:Calcium
keywords: Calcium signaling; Calcium/calmodulin-dependent protein kinase II; Sensory neuron; Voltage-gated calcium channel