Evidence for nicotinic acetylcholine receptor activation in rat cerebellar slices.
Neuronal nicotinic ACh receptor (nAChR) activation is known to enhance glutamate and GABA release in different brain areas. Moreover, nAChRs play an important role in neuronal differentiation. By using the patch-clamp technique, we have investigated the presence of nAChRs in cerebellar granule cells in slices from P5-P14 rats. Application of ACh (1 mM) could elicit a variety of effects. Some cells did not respond at all. In other cells, a somatic current was activated. In a proportion of cells, postsynaptic currents (PSCs), with or without somatic current, were elicited. Somatic nAChRs are likely to be of the alpha(4)beta(2) subtype, but the presence of other subunit combinations (alpha(7)- or beta(4)-containing receptors) cannot be ruled out. The ACh-induced PSCs were glutamatergic in nature. Thus, in a reasonable proportion of cells, nicotinic receptors are present presynaptically. They are likely to be alpha(7) receptors whose activation elicits Glu release via a TTX-sensitive mechanism. Our experiments are the first electrophysiological evidence showing, in a native cerebellar preparation, the presence of nicotinic receptors at the mossy fibre-granule cell synapse at early developmental stages.
De Filippi
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Eli Lilly and Company Limited, Lilly Research Centre, Erl Wood Manor, Sunninghill Road, Windlesham, Surrey GU20 6PH, UK. de_filippi_giovanna@lilly.com
Baldwinson
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Sher
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D000818:Animals; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000378:metabolism*; D017661:Receptors, Presynaptic / Q000819:agonists / Q000037:antagonists & inhibitors
D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D017661:Receptors, Presynaptic