Evidence for the involvement of G-proteins in the generation of the slow poststimulus afterdepolarisation (sADP) induced by muscarinic receptor activation in rat olfactory cortical neurones in vitro.

Postlethwaite, M. and Constanti, A. (2003) Evidence for the involvement of G-proteins in the generation of the slow poststimulus afterdepolarisation (sADP) induced by muscarinic receptor activation in rat olfactory cortical neurones in vitro. Brain Research, 978 (1-2). pp. 124-135. 10.1016/S0006-8993(03)02799-9.

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DOI: 10.1016/S0006-8993(03)02799-9

Abstract

The involvement of G-proteins in generating the slow poststimulus afterdepolarising potential (sADP) induced by muscarinic receptor activation in immature (P10-20) rat olfactory cortical brain slice neurones was investigated under whole-cell patch clamp, using GTP-gamma-S (G-protein activator) or GDP-beta-S (G-protein blocker)-filled electrodes. In control experiments using K methylsulphate electrodes, cell resting potential (V(m)) and spike firing properties were unaffected over 10-15 min recording, although input resistance (R(N)) was slightly increased ( approximately 14%). Oxotremorine-M (OXO-M; 10 microM) produced a reversible slow depolarisation, an increase in R(N) ( approximately 90%) and induction of a slow poststimulus inward tail current (I(ADP)) (measured under voltage clamp at -60 mV) that was sustained during drug exposure (up to 15 min); the amplitude of slow inward rectifier (I(h)) currents activated from -50 mV were also apparently increased. By contrast, in GTP-gamma-S-loaded cells, R(N) was consistently decreased ( approximately 22%) and spike firing threshold (V(th)) was raised ( approximately 5 mV) after 10 min recording. In approximately 60% of loaded cells, a persistent muscarinic slow inward current and I(ADP) were induced by OXO-M; I(h) relaxation amplitude was also significantly decreased. The effects of GTP-gamma-S on R(N), V(th) and I(h) were partly counteracted by adding Ba(2+) (100 microM) to the bathing medium or mimicked by adding baclofen (GABA(B) receptor agonist; 100 microM) to normally-recorded cells. Intracellular GDP-beta-S (up to 30 min) had no effect on cell membrane properties or I(h), but irreversibly blocked the muscarinic slow inward current and I(ADP) induced by OXO-M. We conclude that both muscarinic responses require G-protein-linked transduction mechanisms for their generation.

Item Type:Article
Uncontrolled Keywords:Neurotransmitters, modulators, transporters and receptors, Acetylcholine receptors: muscarinic Whole-cell patch clamp; Brain slice; Rat olfactory cortex neurone; Muscarinic receptor; Slow afterdepolarising tail current (IADP); Slow h-current (Ih); G-proteins; GTP-γ-S, GDP-β-S
Departments, units and centres:Department of Pharmacology > Department of Pharmacology
ID Code:2515
Journal or Publication Title:Brain Research
Deposited By:Library Staff
Deposited On:24 Nov 2011 17:39
Last Modified:24 Nov 2011 17:42

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