Ion channels involved in the presynaptic hyperexcitability induced by herpes virus suis in rat superior cervical ganglion.

Rat superior cervical ganglia infected with herpes virus suis (pseudorabies virus) display a spontaneous bursting activity of still unknown origin. Previous intracellular recordings from the ganglionic neurons combined with pharmacological studies showed that the postganglionic action potentials are induced by acetylcholine release spontaneously from the preganglionic nerve. In this study we investigated whether the acetylcholine release is caused by mechanisms which are dependent on action potentials spontaneously generated on the preganglionic nerve or by mechanisms which occur without any changes in the excitability of presynaptic fibers. Simultaneous intra- and extracellular recordings from the ganglion cells and from the preganglionic nerve, respectively, were performed 32-38 h after the inoculation of herpes virus suis (strain Aujeszky) into the anterior chamber of one eye of the rat. Tetrodotoxin, well known to prevent the generation of action potentials by blocking the fast sodium channels, completely and reversibly abolished, whereas the potassium channel blockers 4-aminopyridine and apamin, enhanced the spontaneous, bursting activity at pre- and postsynaptic levels. The nicotinic receptor antagonist hexamethonium abolished the postsynaptic discharges and reduced the preganglionic activity by 50%. Pre- and postsynaptic electrical activities were suppressed in low calcium Krebs' solution, demonstrating that extracellular calcium is required not only for acetylcholine release but also for triggering the presynaptic action potentials. It is concluded that in the infected ganglia the spontaneous acetylcholine release is due to the generation of action potentials in the preganglionic nerve. Voltage-gated sodium and calcium channels contribute to the presynaptic electrogenesis, while the latter appears to be damped by the activation of voltage- and calcium-dependent potassium channels. Possible factors as well as mechanisms inducing such an increase in excitability are discussed.