Diversity of nicotinic acetylcholine receptors in rat brain. V. alpha-Bungarotoxin-sensitive nicotinic receptors in olfactory bulb neurons and presynaptic modulation of glutamate release.
The presence of functional nicotinic acetylcholine receptors (nAChRs) on cultured neurons of the rat olfactory bulb was evaluated using the whole-cell patch-clamp technique. Application of acetylcholine (ACh) to 78% of the tested olfactory bulb neurons evoked whole-cell currents (referred to as direct response), which are very similar in characteristics to type IA currents. Their peak amplitude increased, while their rise-time and decay-time constants decreased with increasing agonist concentration. In 12% of the neurons, ACh evoked single or multiple miniature postsynaptic currents (referred to as indirect response) for which amplitude, rise time, and decay-time constants were not dependent upon the ACh concentration. Methyllycaconitine (1 nM), a selective competitive antagonist at the alpha-bungarotoxin-sensitive neuronal nAChR, reversibly blocked both responses, whereas 6-cyano-7-nitroquinoxaline-2,3-di-one (10 microM) reversibly blocked only the indirect responses. Whereas tetrodotoxin (0.2-2 microM) failed to affect the indirect response, Ca(+2)-free, Mg(+2)-containing external solution decreased reversibly and significantly the frequency of ACh-evoked miniature postsynaptic currents. The pharmacology and kinetics of the two types of responses are consistent with the existence in the olfactory bulb neurons of alpha-bungarotoxin-sensitive nAChRs at both postsynaptic and presynaptic sites, the presynaptic receptors being located on glutamatergic synapses where they modulate the release of the transmitter. The dimensions of the soma and dendrites of the neurons suggest that the direct response is obtained from periglomerular and/or granular neurons, and the indirect response from short-axon and/or external tufted cells. The present results suggest that 1) nicotinic synaptic transmission could play an important role in modulating the bulbar output at the glomerular level, and 2) a presynaptic modulatory effect is one of the functions for the alpha-bungarotoxin-sensitive nAChRs in the mammalian central nervous system.
Alkondon
M
M
Department of Pharmacology and Experimental Therapeutics, University of Maryland, School of Medicine, Baltimore, USA.
Rocha
E S
ES
Maelicke
A
A
Albuquerque
E X
EX
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology; D002478:Cells, Cultured; D002799:Cholinergic Fibers / Q000502:physiology; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D005971:Glutamates / Q000502:physiology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D009830:Olfactory Bulb / Q000166:cytology / Q000502:physiology*; D051381:Rats; D011978:Receptors, Nicotinic / Q000145:classification* / Q000187:drug effects / Q000502:physiology; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission
D002038:Bungarotoxins; D005971:Glutamates; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D000109:Acetylcholine