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Chronic-moderate ethanol exposure of L(tk-) cells expressing ? 4? 3? GABAA receptors reduces potency of allopregnanolone potentiation of GABA-evoked inward currents: Possible role of PKC

Barrett, I.D., Kelley, Stephen P. (2012) Chronic-moderate ethanol exposure of L(tk-) cells expressing ? 4? 3? GABAA receptors reduces potency of allopregnanolone potentiation of GABA-evoked inward currents: Possible role of PKC. In: British Pharmacological Society Winter Meeting, 19th December 2012, London. (KAR id:53233)

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Abstract

Aim: To investigate the effect of chronic-moderate ethanol (CME) treatment upon direct activation and allosteric modulation of GABAA receptors, and to assess the sensitivity of these parameters to PKC inhibition in control and ethanol-treated cells.

Results: Expression of ?4 subunits was reduced 35% (P<0.05) in ethanol-treated cells but the efficacy (control: 9.04±0.93 pA/pF, n=41, CME: 6.39±1.16 pA/pF, n=13, P>0.05) and pEC50 (control: 6.18±0.04, n=13, CME: 6.17±0.04, n=4, P>0.05) of GABA were unchanged. CphC increased the GABA pEC50 relative to control (6.62±0.08, n=3, P<0.001) but had no effect upon responses at pEC20 GABA. Following CME, the potency of GABA was unaltered in the presence of CphC.

The ALLO pEC50 in control cells (6.23±0.05, n=19) was unaffected by CphC. Following CME, the potency of ALLO was reduced (5.68±0.06, n=9, P<0.001) but was enhanced in the presence of CphC, which restored potency almost back to control levels (5.94±0.09, n=5, P<0.05 relative to control).

Discussion: CME of un-induced L(tk-) cells was sufficient to alter sensitivity of ?4?3? receptor function to alterations of the balance of phosphorylation induced by CphC. The increased expression of PKC? after CME may have been directly related to the absence of effect of CphC upon GABA potency. As direct interaction of GABAA receptors with PKC? has not been determined, the effects observed for potency and efficacy of ALLO following CME may be indicative of changes to the phosphorylation of accessory proteins or other PKC isoforms by PKC?.

Item Type: Conference or workshop item (Poster)
Subjects: Q Science > QP Physiology (Living systems)
R Medicine > RM Therapeutics. Pharmacology
Divisions: Divisions > Division of Natural Sciences > Medway School of Pharmacy
Depositing User: Stephen Kelley
Date Deposited: 13 Dec 2015 04:42 UTC
Last Modified: 16 Feb 2021 13:31 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/53233 (The current URI for this page, for reference purposes)
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