DIVERSITY OF NICOTINIC ACETYLCHOLINE-RECEPTORS IN RAT-BRAIN .5. ALPHA-BUNGAROTOXIN-SENSITIVE NICOTINIC RECEPTORS IN OLFACTORY-BULB NEURONS AND PRESYNAPTIC MODULATION OF GLUTAMATE RELEASE
M. Alkondon et al., DIVERSITY OF NICOTINIC ACETYLCHOLINE-RECEPTORS IN RAT-BRAIN .5. ALPHA-BUNGAROTOXIN-SENSITIVE NICOTINIC RECEPTORS IN OLFACTORY-BULB NEURONS AND PRESYNAPTIC MODULATION OF GLUTAMATE RELEASE, The Journal of pharmacology and experimental therapeutics, 278(3), 1996, pp. 1460-1471
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) t
o 78% of the tested olfactory bulb neurons evoked whole-cell currents
(referred to as direct response), which are very similar in characteri
stics 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 mi
niature postsynaptic currents (referred to as indirect response) for w
hich amplitude, rise time, and decay-time constants were not dependent
upon the ACh concentration. Methyllycaconitine (1 nM), a selective co
mpetitive antagonist at the the alpha-bungarotoxin-sensitive neuronal
nAChR, reversibly blocked both responses, whereas 6-cyano-T-nitroquino
xaline-2,3-dione (10 mu M) reversibly blocked only the indirect respon
ses. Whereas tetradotoxin (0.2-2 mu M) failed to affect the indirect r
esponse, Ca++-free, Mg++-containing external solution decreased revers
ibly and significantly the frequency of ACh-evoked miniature postsynap
tic currents. The pharmacology and kinetics of the two types of respon
ses are consistent with the existence in the olfactory bulb neurons of
alpha-bungarotoxin-sensitive nAChRs at both postsynaptic and presynap
tic sites, the presynaptic receptors being located on glutamatergic sy
napses where they modulate the release of the transmitter. The dimensi
ons of the soma and dendrites of the neurons suggest that the direct r
esponse is obtained from periglomerular and/or granular neurons, and t
he 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 glomeru
lar level, and 2) a presynaptic modulatory effect is one of the functi
ons for the alpha-bungarotoxin-sensitive nAChRs in the mammalian centr
al nervous system.