NERVE-TERMINAL CURRENTS INDUCED BY AUTORECEPTION OF ACETYLCHOLINE-RELEASE

The activation of autoreceptors is known to be important in the modula tion of presynaptic transmitter secretion in peripheral and central ne urons. Using whole-cell recordings made from the free growth cone of m yocyte-contact motoneurons of Xenopus cell cultures, we have observed spontaneous nerve terminal currents (NTCs). These spontaneous NTCs are blocked by d-tubocurarine (d-TC) and alpha-bungarotoxin (alpha-BuTx), indicating that endogenously released acetylcholine (ACh) can produce substantial membrane depolarization in the nerve terminals. Local app lication of NMDA to the growth cone increased the frequency of spontan eous NTCs. When the electrical stimulations were applied at the soma t o initiate evoked-release of ACh, evoked ACh-induced potentials were r ecorded in the nerve terminals, which were inhibited by d-TC and hexam ethonium but not by atropine. Replacement of normal Ringer's solution with high-Mg2+, low-Ca2+ solution also reversibly inhibited evoked ACh -induced potentials. The possible regulatory role of presynaptic nicot inic autoreceptors on the synaptic transmission was also examined. Whe n the innervated myocyte was whole-cell voltage-clamped to record syna ptic currents, application of hexamethonium inhibited the amplitude of evoked synaptic currents at a higher degree than that of iontophoreti c ACh-induced currents. Furthermore, hexamethonium markedly reduced th e frequency of spontaneous synaptic currents at high-activity synapses . Pretreatment of neurons with alpha-BuTx also inhibited the evoked sy naptic currents in manipulated synapses. These results suggest that AC h released spontaneously or by electrical stimulation may act on the p resynaptic nicotinic autoreceptors of the same nerve terminals to prod uce membrane potential change and to regulate synaptic transmission.