Bidirectional control of BK channel open probability by CAMKII and PKC in medial vestibular nucleus neurons
- 1 April 2011
- journal article
- research article
- Published by American Physiological Society in Journal of Neurophysiology
- Vol. 105 (4), 1651-1659
- https://doi.org/10.1152/jn.00058.2011
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 Ca2+ 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 Ca2+/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.Keywords
This publication has 79 references indexed in Scilit:
- Mechanisms of Sustained High Firing Rates in Two Classes of Vestibular Nucleus Neurons: Differential Contributions of Resurgent Na, Kv3, and BK CurrentsJournal of Neurophysiology, 2010
- Activity-dependent relocation of the axon initial segment fine-tunes neuronal excitabilityNature, 2010
- Dual role of protein kinase C on BK channel regulationProceedings of the National Academy of Sciences of the United States of America, 2010
- Biphasic Somatic A-Type K+ Channel Downregulation Mediates Intrinsic Plasticity in Hippocampal CA1 Pyramidal NeuronsPLOS ONE, 2009
- Supramolecular Assemblies and Localized Regulation of Voltage-Gated Ion ChannelsPhysiological Reviews, 2009
- Blocking the BK channel impedes acquisition of trace eyeblink conditioningLearning & Memory, 2009
- The BK-mediated fAHP is modulated by learning a hippocampus-dependent taskProceedings of the National Academy of Sciences of the United States of America, 2008
- Regulation of Dendritic Excitability by Activity-Dependent Trafficking of the A-Type K+ Channel Subunit Kv4.2 in Hippocampal NeuronsNeuron, 2007
- High-conductance potassium channels of the SLO familyNature Reviews Neuroscience, 2006
- Control of Memory Formation Through Regulated Expression of a CaMKII TransgeneScience, 1996