Pharmacological characterization of a non-inactivating outward current observed in mouse cerebellar Purkinje neurones.

Bushell, Trevor J. and Clarke, Catherine E. and Mathie, Alistair and Robertson, Brian (2002) Pharmacological characterization of a non-inactivating outward current observed in mouse cerebellar Purkinje neurones. British Journal of Pharmacology, 135 (3). pp. 705-712. ISSN 0007-1188 . (The full text of this publication is not available from this repository)

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Abstract

Whole-cell patch clamp recordings were used to investigate the properties of a non-inactivating outward current observed in mouse cerebellar Purkinje neurones at a holding potential of -20 mV. Increasing the external potassium (K(+)) concentration from 3 mM to 20 mM produced a rightward shift in the observed reversal potential of approximately 30 mV or approximately 40 mV for a K(+)-or a caesium (Cs(+))-based intracellular solution respectively, indicating the outward current was a K(+) current. The outward current was partially inhibited by the K(+) channel blocker, tetraethylammonium (TEA; IC(50)=0.15 mM). Subsequently, the background or TEA-insensitive current was measured in the presence of 1 mM TEA. The background current was reversibly inhibited by barium (Ba(2+); 300 microM, 50%) and potentiated by the application of arachidonic acid (AA; 1 mM, 62%). The volatile anaesthetic, halothane (1 mM), and the neuroprotectant, riluzole (500 microM), both reversibly inhibited the background current by 54% and 36% respectively. The background current was insensitive to changes in both intracellular and extracellular acidification. The GABA(B) and mu-opioid receptor agonists, baclofen and [D-Ala(2), N-MePhe(4)-Gly-ol(5)] enkephalin (DAMGO) both reversibly potentiated the outward current by 42% and 26% respectively. In contrast, the metabotropic glutamate receptor and acetylcholine receptor agonists, (S)-3,5-dihydroxyphenylglycine (DHPG) and muscarine both reversibly inhibited the outward current by 48% and 42% respectively. These data suggest that cerebellar Purkinje neurones possess a background current which shares several properties with recently cloned two-pore K(+) channels, particularly THIK-1.

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: 09 Mar 2009 23:37
Last Modified: 14 May 2014 14:10
Resource URI: http://kar.kent.ac.uk/id/eprint/5688 (The current URI for this page, for reference purposes)
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