Differential modulation of nicotinic acetylcholine receptor subtypes and synaptic transmission in chick sympathetic ganglia by PGE(2)

The diversity of neuronal nicotinic acetylcholine receptors (nAChRs) is lik ely an important factor in the modulation of synaptic transmission by acety lcholine and nicotine. We have tested whether postsynaptic nAChRs are modul ated in a subtype-specific manner by prostaglandin E-2 (PGE(2)), a regulato r of neuronal excitability in both the central and peripheral nervous syste ms, and examined the effects of PGE(2) on nicotinic transmission. Somatoden dritic nAChRs in chick lumbar sympathetic ganglia include four nAChR subtyp es distinguished on the basis of conductance and kinetic profile. Nanomolar PGE(2) applied to the extrapatch membrane differentially regulates opening probability (Po), frequency and the opening duration of each nAChR channel subtype in cell-attached patches. PGE(2) decreases the Po of the predomina nt nAChR subtype (36 pS) and significantly increases Po and open duration o f the 23 pS subtype. The 23 pS subtype is gated by the alpha7-selective ago nist choline, and choline-gated currents are inhibited by alpha -bungarotox in. To examine whether PGE(2) modulates nAChRs at synaptic sites, we studie d the effects of PGE(2) on amplitude and decay of synaptic currents in visc eral motoneuron-sympathetic neuron co-cultures. PGE(2) significantly decrea ses the amplitude of miniature excitatory postsynaptic currents (mEPSCs), c onsistent with the predominant inhibition by PGE(2) of all but the 23 pS su btype. The time constant of mEPSCs at PGE(2)-treated synapses is prolonged, which is also consistent with an increased contribution of the longer open duration of the 23 pS nAChR subtype with PGE(2) treatment. To examine the presynaptic effect of PGE(2), nanomolar nicotine was used. Nicotine induces facilitation of synaptic transmission by increasing mEPSC frequency, an ac tion thought to involve presynaptic, alpha7-containing nAChRs. In the prese nce of PGE(2), nicotine-induced synaptic facilitation persists. Thus the ne t effect of PGE(2) is to alter the profile of nAChRs contributing to synapt ic transmission from larger conductance, briefer opening channels to smalle r conductance, longer opening events. This subtype-specific modulation of n AChRs by PGE(2) may provide a mechanism for selective activation and suppre ssion of synaptic pathways mediated by different nAChR subtype(s) at both p re- and postsynaptic sites.