title: Bidirectional control of BK channel open probability by CAMKII and PKC in medial vestibular nucleus neurons.
abstract: Large conductance K(+) (BK) channels are a key determinant of neuronal excitability. Medial vestibular nucleus (MVN) neurons regulate eye movements to ensure image stabilization during head movement, and changes in their intrinsic excitability may play a critical role in plasticity of the vestibulo-ocular reflex. Plasticity of intrinsic excitability in MVN neurons is mediated by kinases, and BK channels influence excitability, but whether endogenous BK channels are directly modulated by kinases is unknown. Double somatic patch-clamp recordings from MVN neurons revealed large conductance potassium channel openings during spontaneous action potential firing. These channels displayed Ca(2+) and voltage dependence in excised patches, identifying them as BK channels. Recording isolated single channel currents at physiological temperature revealed a novel kinase-mediated bidirectional control in the range of voltages over which BK channels are activated. Application of activated Ca(2+)/calmodulin-dependent kinase II (CAMKII) increased BK channel open probability by shifting the voltage activation range towards more hyperpolarized potentials. An opposite shift in BK channel open probability was revealed by inhibition of phosphatases and was occluded by blockade of protein kinase C (PKC), suggesting that active PKC associated with BK channel complexes in patches was responsible for this effect. Accordingly, direct activation of endogenous PKC by PMA induced a decrease in BK open probability. BK channel activity affects excitability in MVN neurons and bidirectional control of BK channels by CAMKII, and PKC suggests that cellular signaling cascades engaged during plasticity may dynamically control excitability by regulating BK channel open probability.
authors.affiliation: Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, San Diego, CA 92037, USA.
authors.forename: Ingrid
authors.initials: I
authors.lastname: van Welie
authors.forename: Sascha
authors.initials: S
authors.lastname: du Lac
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001831:Body Temperature / Q000502:physiology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000502:physiology*; D005260:Female; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000502:physiology*; D014726:Vestibular Nuclei / Q000502:physiology*
chemical_list: D051036:Large-Conductance Calcium-Activated Potassium Channels; D011493:Protein Kinase C; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2