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Task-3 Two-Pore Domain Potassium Channels Enable Sustained High-Frequency Firing in Cerebellar Granule Neurons

Brickley, Stephen G, Aller, M Isabel, Sandu, Cristina, Veale, Emma L., Alder, Felicity G, Sambi, Harvinder, Mathie, Alistair, Wisden, William (2007) Task-3 Two-Pore Domain Potassium Channels Enable Sustained High-Frequency Firing in Cerebellar Granule Neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience, 27 (35). pp. 9329-40. ISSN 1529-2401. (doi:10.1523/JNEUROSCI.1427-07.2007) (KAR id:75924)

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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.

Item Type: Article
DOI/Identification number: 10.1523/JNEUROSCI.1427-07.2007
Subjects: Q Science
Divisions: Divisions > Division of Natural Sciences > Medway School of Pharmacy
Depositing User: Emma Veale
Date Deposited: 21 Aug 2019 12:04 UTC
Last Modified: 16 Nov 2021 10:26 UTC
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