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The Journal of Neuroscience, August 29, 2007, 27(35):9329-9340; doi:10.1523/JNEUROSCI.1427-07.2007

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Cellular/Molecular
TASK-3 Two-Pore Domain Potassium Channels Enable Sustained High-Frequency Firing in Cerebellar Granule Neurons

Stephen G. Brickley,^1 * M. Isabel Aller,^2 * Cristina Sandu,² Emma L. Veale,¹ Felicity G. Alder,¹ Harvinder Sambi,¹ Alistair Mathie,¹ and William Wisden²

¹Biophysics Group, Division of Cell and Molecular Biology, Imperial College London, London SW7 2AZ, United Kingdom, and ²Department of Clinical Neurobiology, University of Heidelberg, Heidelberg 69120, Germany

Correspondence should be addressed to Stephen G. Brickley, Biophysics Group, Division of Cell and Molecular Biology, Imperial College London, London SW7 2AZ, UK. Email: s.brickley{at}imperial.ac.uk

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.

Key words: accommodation; action potential; cerebellum; excitability; granule cell; potassium channels

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Received March 30, 2007; revised June 12, 2007; accepted July 2, 2007.

Correspondence should be addressed to Stephen G. Brickley, Biophysics Group, Division of Cell and Molecular Biology, Imperial College London, London SW7 2AZ, UK. Email: s.brickley{at}imperial.ac.uk

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