期刊
JOURNAL OF NEUROPHYSIOLOGY
卷 116, 期 5, 页码 2114-2124出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/jn.00446.2016
关键词
spinal cord; membrane properties; XE991; retigabine; voltage threshold
资金
- National Institutes of Health [R15 HD-075207, P20 GM-103653]
- Army Research Office [W911NF-15-1-0559]
KCNQ/K(v)7 channels form a slow noninactivating K+ current, also known as the M current. They activate in the subthreshold range of membrane potentials and regulate different aspects of excitability in neurons of the central nervous system. In spinal motoneurons (MNs), KCNQ/K(v)7 channels have been identified in the somata, axonal initial segment, and nodes of Ranvier, where they generate a slow, noninactivating, K+ current sensitive to both muscarinic receptor-mediated inhibition and KCNQ/K(v)7 channel blockers. In this study, we thoroughly re-evaluated the function of up-and downregulation of KCNQ/K(v)7 channels in mouse immature spinal MNs. Using electrophysiological techniques together with specific pharmacological modulators of the activity of KCNQ/K(v)7 channels, we show that enhancement of the activity of these channels decreases the excitability of spinal MNs in mouse neonates. This action on MNs results from a combination of hyperpolarization of the resting membrane potential, a decrease in the input resistance, and depolarization of the voltage threshold. On the other hand, the effect of inhibition of KCNQ/K(v)7 channels suggested that these channels play a limited role in regulating basal excitability. Computer simulations confirmed that pharmacological enhancement of KCNQ/K(v)7 channel activity decreases excitability and also suggested that the effects of inhibition of KCNQ/K(v)7 channels on the excitability of spinal MNs do not depend on a direct effect in these neurons but likely on spinal cord synaptic partners. These results indicate that KCNQ/K(v)7 channels have a fundamental role in the modulation of the excitability of spinal MNs acting both in these neurons and in their local presynaptic partners.
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