Modifying the subunit composition of TASK channels alters the modulation of a leak conductance in cerebellar granule neurons.

Aller, M. Isabel and Veale, Emma L. and Linden, Anni-Maija and Sandu, Cristina and Schwaninger, Markus and Evans, Louisa J. and Korpi, Esa R. and Mathie, Alistair and Wisden, William and Brickley, Stephen G. (2005) Modifying the subunit composition of TASK channels alters the modulation of a leak conductance in cerebellar granule neurons. Journal of Neuroscience, 25 (49). pp. 11455-11467. ISSN 0270-6474. (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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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 These results suggest that a TASK-1-containing channel population has been replaced by a homodimeric TASK-3 population in the TASK-1 knock-out.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
Subjects: Q Science > QP Physiology (Living systems)
Divisions: Faculties > Science Technology and Medical Studies > Medway School of Pharmacy
Depositing User: Alistair Mathie
Date Deposited: 15 Mar 2009 18:01
Last Modified: 11 Jun 2014 10:53
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