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This Article Full Text Full Text (PDF) All Versions of this Article: 563/3/765    most recent jphysiol.2004.080192v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Stephens, G. J Articles by Mochida, S. Search for Related Content PubMed PubMed Citation Articles by Stephens, G. J Articles by Mochida, S.

¹ Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK
² Department of Physiology, Tokyo Medical University, Tokyo 160-8402, Japan

The activation of presynaptic G protein-coupled receptors (GPCRs) is widely reported to inhibit transmitter release; however, the lack of accessibility of many presynaptic terminals has limited direct analysis of signalling mediators. We studied GPCR-mediated inhibition of fast cholinergic transmission between superior cervical ganglion neurones (SCGNs) in culture. The adrenoceptor agonist noradrenaline (NA) caused a dose-related reduction in evoked excitatory postsynaptic potentials (EPSPs). NA-induced EPSP decrease was accompanied by effects on the presynaptic action potential (AP), reducing AP duration and amplitude of the after-hyperpolarization (AHP), without affecting the pre- and postsynaptic membrane potential. All effects of NA were blocked by yohimbine and synaptic transmission was reduced by clonidine, consistent with an action at presynaptic 2-adrenoceptors. NA-induced inhibition of transmission was sensitive to pre-incubation of SCGNs with pertussis toxin (PTX), implicating the involvement of G_i/oß subunits. Expression of G transducin, an agent which sequesters G protein ß (Gß) subunits, in the presynaptic neurone caused a time-dependent attenuation of NA-induced inhibition. Injection of purified Gß subunits into the presynaptic neurone inhibited transmission, and also reduced the AHP amplitude. Furthermore, NA-induced inhibition was occluded by pre-injection of Gß subunits. The Ca²⁺ channel blocker Cd²⁺ mimicked NA effects on transmitter release. Cd²⁺, NA and Gß subunits also inhibited somatic Ca²⁺ current. In contrast to effects on AP-evoked transmitter release, NA had no clear action on AP-independent EPSPs induced by hypertonic solutions. These results demonstrate that Gß subunits functionally mediate inhibition of transmitter release by 2-adrenoceptors and represent important regulators of synaptic transmission at mammalian presynaptic terminals.

(Received 3 December 2004; accepted after revision 14 January 2005; first published online 20 January 2005)
Corresponding author G. Stephens: Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK. Email: g.stephens{at}ucl.ac.uk

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