Effects of an indene-derivative, TN-871, on synaptic transmission in a sympathetic ganglion: presynaptic actions on neurotransmitter release.

Intracellular recordings were made from bullfrog sympathetic ganglion cells to elucidate effects of 2-n-butyl-1-(4-methylpiperazinyl)-5,6-methylenedioxyindene.2 HCl (TN-871) on synaptic transmission. TN-871 at 30 nM augmented cholinergic nicotinic fast excitatory postsynaptic potentials (fast EPSPs), whereas the drug at 3 microM reversibly depressed them, without affecting acetylcholine-induced depolarizations. TN-871 did not affect active and passive electrical properties of the ganglion cells. The quantal analysis method was applied to the fast EPSPs in a 0.54 mM Ca2+/7.56 mM Mg2+ Ringer's solution. The mean quantal content was significantly increased by TN-871 at 30 nM but significantly decreased at 3 microM. TN-871 at 300 nM either increased or decreased the mean quantal content. The mean quantal size of the fast EPSPs was not changed by TN-871 at the concentrations examined. Fast EPSPs in a 0.99 mM Ca2+/4.86 mM Mg2+ Ringer's solution were not affected by nicardipine, but were inhibited in amplitude by omega-conotoxin in a concentration-dependent manner. It is likely that TN-871, in high concentrations, might block omega-conotoxin-sensitive N-type calcium channels in the presynaptic terminals. These results indicate that TN-871 modulates transmitter release from preganglionic nerve terminals without changing the postsynaptic sensitivity of the ganglion cells to ACh.