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A functional role for the two-pore domain potassium channel TASK-1 in cerebellar granule neurons.

Millar, Julie A., Barratt, Lynne, Southan, Andrew P., Page, Karen M., Fyffe, Robert E., Robertson, Brian, Mathie, Alistair (2000) A functional role for the two-pore domain potassium channel TASK-1 in cerebellar granule neurons. Proceedings of the National Academy of Sciences of the United States of America, 97 (7). pp. 3614-8. ISSN 0027-8424. (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)

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. (Contact us about this Publication)

Abstract

Cerebellar granule neurons (CGNs) are one of the most populous cells in the mammalian brain. They express an outwardly rectifying potassium current, termed a "standing-outward" K(+) current, or IK(SO), which does not inactivate. It is active at the resting potential of CGNs, and blocking IK(SO) leads to cell depolarization. IK(SO) is blocked by Ba(2+) ions and is regulated by activation of muscarinic M(3) receptors, but it is insensitive to the classical broad-spectrum potassium channel blocking drugs 4-aminopyridine and tetraethylammonium ions. The molecular nature of this important current has yet to be established, but in this study, we provide strong evidence to suggest that IK(SO) is the functional correlate of the recently identified two-pore domain potassium channel TASK-1. We show that IK(SO) has no threshold for activation by voltage and that it is blocked by small extracellular acidifications. Both of these are properties that are diagnostic of TASK-1 channels. In addition, we show that TASK-1 currents expressed in Xenopus oocytes are inhibited after activation of endogenous M(3) muscarinic receptors. Finally, we demonstrate that mRNA for TASK-1 is found in CGNs and that TASK-1 protein is expressed in CGN membranes. This description of a functional two-pore domain potassium channel in the mammalian central nervous system indicates its physiological importance in controlling cell excitability and how agents that modify its activity, such as agonists at G protein-coupled receptors and hydrogen ions, can profoundly alter both the neuron's resting potential and its excitability.

Item Type: Article
Subjects: Q Science > QP Physiology (Living systems)
Divisions: Faculties > Sciences > Medway School of Pharmacy
Depositing User: Alistair Mathie
Date Deposited: 06 Mar 2014 17:09 UTC
Last Modified: 29 May 2019 11:57 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/38628 (The current URI for this page, for reference purposes)
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