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 likely an important factor in the modulation of synaptic transmission by acetylcholine and nicotine. We have tested whether postsynaptic nAChRs are modulated in a subtype-specific manner by prostaglandin E(2) (PGE(2)), a regulator of neuronal excitability in both the central and peripheral nervous systems, and examined the effects of PGE(2) on nicotinic transmission. Somatodendritic nAChRs in chick lumbar sympathetic ganglia include four nAChR subtypes 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 predominant nAChR subtype (36 pS) and significantly increases Po and open duration of the 23 pS subtype. The 23 pS subtype is gated by the alpha 7-selective agonist choline, and choline-gated currents are inhibited by alpha-bungarotoxin. To examine whether PGE(2) modulates nAChRs at synaptic sites, we studied the effects of PGE(2) on amplitude and decay of synaptic currents in visceral motoneuron-sympathetic neuron co-cultures. PGE(2) significantly decreases the amplitude of miniature excitatory postsynaptic currents (mEPSCs), consistent with the predominant inhibition by PGE(2) of all but the 23 pS subtype. 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 action thought to involve presynaptic, alpha 7-containing nAChRs. In the presence of PGE(2), nicotine-induced synaptic facilitation persists. Thus the net effect of PGE(2) is to alter the profile of nAChRs contributing to synaptic transmission from larger conductance, briefer opening channels to smaller conductance, longer opening events. This subtype-specific modulation of nAChRs by PGE(2) may provide a mechanism for selective activation and suppression of synaptic pathways mediated by different nAChR subtype(s) at both pre- and postsynaptic sites.