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

M. I. Aller, E. L. Veale, A. M. Linden, C. Sandu, M. Schwaninger, L. J. Evans, E. R. Korpi, A. Mathie, William Wisden, S. G. Brickley

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    Abstract

    Two-pore domain potassium (K-2P) channel expression is believed to underlie the developmental emergence of a potassium leak conductance [IK(SO)] in cerebellar granule neurons (CGNs), suggesting that K-2P function is an important determinant of the input conductance and resting membrane potential. To investigate the role that different K-2P channels may play in the regulation of CGN excitability, we generated a mouse lacking TASK-1, a K-2P 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 I-K(SO) by extracellular Zn2+, ruthenium red, and H+ was altered. The I-K(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 These results suggest that a TASK-1-containing channel population has been replaced by a homodimeric TASK-3 population in the TASK-1 knock-out.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 I-K(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+.

    Original languageEnglish
    Pages (from-to)11455-11467
    Number of pages12
    JournalJournal of Neuroscience
    Volume25
    Issue number49
    DOIs
    Publication statusPublished - Dec 2005

    Keywords

    • potassium channels
    • cerebellum
    • motor control
    • patch-clamp
    • knock-out mice
    • excitability
    • DOMAIN POTASSIUM CHANNEL
    • BACKGROUND K+ CHANNEL
    • FUNCTIONAL EXPRESSION
    • RECEPTOR ACTIVATION
    • GABA(A) RECEPTORS
    • CELLS
    • RAT
    • MICE
    • INHIBITION
    • PHARMACOLOGY

    Cite this

    Aller, M. I., Veale, E. L., Linden, A. M., Sandu, C., Schwaninger, M., Evans, L. J., ... Brickley, S. 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), 11455-11467. https://doi.org/10.1523/JNEUROSCI.3153-05.2005