Brickley, S.G. and Aller, M.I. and Sandu, C. and Veale, E.L. and Alder, F.G. and Sambi, H. and Mathie, A.A. and Wisden, W. (2007) TASK-3 two-pore domain potassium channels enable sustained high-frequency firing in cerebellar granule neurons. Journal of Neuroscience, 27 (35). pp. 9329-9340. ISSN 0270-6474 .
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The ability of neurons, such as cerebellar granule neurons (CGNs), to fire action potentials (APs) at high frequencies during sustained depolarization is usually explained in relation to the functional properties of voltage-gated ion channels. Two-pore domain potassium (K(2P)) channels are considered to simply hyperpolarize the resting membrane potential (RMP) by increasing the potassium permeability of the membrane. However, we find that CGNs lacking the TASK-3 type K(2P) channel exhibit marked accommodation of action potential firing. The accommodation phenotype was not associated with any change in the functional properties of the underlying voltage-gated sodium channels, nor could it be explained by the more depolarized RMP that resulted from TASK-3 channel deletion. A functional rescue, involving the introduction of a nonlinear leak conductance with a dynamic current clamp, was able to restore wild-type firing properties to adult TASK-3 knock-out CGNs. Thus, in addition to the accepted role of TASK-3 channels in limiting neuronal excitability, by increasing the resting potassium conductance TASK-3 channels also increase excitability by supporting high-frequency firing once AP threshold is reached.
|Uncontrolled keywords:||accommodation; action potential; cerebellum; excitability; granule cell; potassium channels|
|Subjects:||R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Q Science > QP Physiology (Living systems)
|Divisions:||Faculties > Science Technology and Medical Studies > Medway School of Pharmacy|
|Depositing User:||Alistair Mathie|
|Date Deposited:||13 Aug 2009 14:23|
|Last Modified:||14 Jan 2010 14:21|
|Resource URI:||http://kar.kent.ac.uk/id/eprint/5613 (The current URI for this page, for reference purposes)|
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