Modulation of Kv3.4 channel N-type inactivation by protein kinase C shapes the action potential in dorsal root ganglion neurons

摘要: 2GraduatePrograminNeuroscienceand 3 DepartmentofPathology,AnatomyandCellBiology,JeffersonMedicalCollegeofThomasJeffersonUniversity, Philadelphia, PA 19107, USA Non-technicalsummary The orchestrated activity of an ensemble voltage-gated ion channels determines the initiation, shape and duration action potential in excitable cells. In primarypain-sensingneurons,thisensembleincludesahighvoltage-activatedpotassiumchannel. However,itsmolecularidentity,functionandmodulationwereunknown.Here,weshowthatthe rapidly inactivating Kv3.4 channel underlying high voltage-activated potassium current is a major determinant repolarization. Furthermore, we found that physiological activation protein kinase C dramatically slows inactivation, which enhances channel’s ability to influence Based on these results earlier work,weconcludethatphosphorylationoftheKv3.4channelinactivationgateisamechanismby whichpain-sensingneuronsshapeactionpotentialrepolarization.Thismodulationwillinfluence Ca 2+ -dependent processes play vital roles nociception might become deregulated chronic pain.