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Modifying the Subunit Composition of Task Channels Alters the Modulation of a Leak Conductance in Cerebellar Granule Neurons

Aller, M Isabel, Veale, Emma L., Linden, Anni-Maija, Sandu, Cristina, Schwaninger, Markus, Evans, Louisa J, Korpi, Esa R, Mathie, Alistair, Wisden, William, Brickley, Stephen G and others. (2005) Modifying the Subunit Composition of Task Channels Alters the Modulation of a Leak Conductance in Cerebellar Granule Neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience, 25 (49). pp. 11455-67. ISSN 1529-2401. (doi:10.1523/JNEUROSCI.3153-05.2005) (KAR id:75929)

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http://dx.doi.org/10.1523/JNEUROSCI.3153-05.2005

Abstract

Two-pore domain potassium (K2P) channel expression is believed to underlie the developmental emergence of a potassium leak conductance [IK(SO)] in cerebellar granule neurons (CGNs), suggesting that K2P function is an important determinant of the input conductance and resting membrane potential. To investigate the role that different K2P channels may play in the regulation of CGN excitability, we generated a mouse lacking TASK-1, a K2P channel known to have high expression levels in CGNs. In situ hybridization and real-time PCR studies in wild-type and TASK-1 knock-outs (KOs) demonstrated that the expression of other K2P channels was unaltered in CGNs. TASK-1 knock-out mice were healthy and bred normally but exhibited compromised motor performance consistent with altered cerebellar function. Whole-cell recordings from adult cerebellar slice preparations revealed that the resting excitability of mature CGNs was no different in TASK-1 KO and littermate controls. However, the modulation of IK(SO) by extracellular Zn2+, ruthenium red, and H+ was altered. The IK(SO) recorded from TASK-1 knock-out CGNs was no longer sensitive to alkalization and was blocked by Zn2+ and ruthenium red. These results suggest that a TASK-1-containing channel population has been replaced by a homodimeric TASK-3 population in the TASK-1 knock-out. These data directly demonstrate that TASK-1 channels contribute to the properties of IK(SO) in adult CGNs. However, TASK channel subunit composition does not alter the resting excitability of CGNs but does influence sensitivity to endogenous modulators such as Zn2+ and H+.

Item Type: Article
DOI/Identification number: 10.1523/JNEUROSCI.3153-05.2005
Divisions: Faculties > Sciences > Medway School of Pharmacy
Depositing User: Emma Veale
Date Deposited: 21 Aug 2019 12:17 UTC
Last Modified: 23 Jan 2020 04:16 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/75929 (The current URI for this page, for reference purposes)
Veale, Emma L.: https://orcid.org/0000-0002-6778-9929
Mathie, Alistair: https://orcid.org/0000-0001-6094-2890
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