Ionic Basis of Inhibitory Presynaptic Modulation in Rat Cortical Synaptosomes

Abstract

We have investigated the possibility that, regardless of the involvement of a second messenger system, the ultimate effect of presynaptic, receptor-activated inhibitory modulation is the opening of a K channel. With the consequent hyperpolarization of the terminal, less Ca2+ would enter and this would result in the observed diminished release of a neurotransmitter. This possibility was explored utilizing rat cortical synaptosomes that were prelabeled with either 86Rb or [3H]acetylcholine, depolarizing with either K+ or veratridine, and measuring either efflux of 86Rb or release of [3H]acetylcholine in the presence or absence of inhibitory presynaptic modulators. The modulating agents used were 2-chloroadenosine, carbamylcholine, clonidine, and morphine. In all instances, these agents promoted an increased efflux of 86Rb, indicating hyperpolarization, and decreased release of acetylcholine. These results are compatible with our suggestion that an increase in K conductance may be responsible for presynaptic inhibition of the release of neurotransmitters.

A Decrease in [Ca2+]c but not in cAMP Mediates L‐AP4 Inhibition of Glutamate Release: PKC‐mediated Suppression of this Inhibitory Pathway

“…Thus, a reduction in Ca2+ entry into the nerve terminal by Ca2+ channel toxins decreases glutamate release (Pocock and Nicholls, 1992;Turner et al, 1992). In addition, receptormediated inhibition of neurotransmitter release can result either from inhibition of Ca2' channels coupled to glutamate exocytosis (Banie and Nicholls, 1993) or from the activation of presynaptic Kf channels (Zoltay and Cooper, 1990). Our results indicate that L -A P~ reduces glutamate release under the clamped depolarization produced by KCI, in which Kf channel modulation of glutamate release is ineffective.…”

12‐Lipoxygenase Products Attenuate the Glutamate Release and Ca2+ Accumulation Evoked by Depolarization of Hippocampal Mossy Fiber Nerve Endings

“…The inhibitory effects of 12(S)-HETE may depend on its ability to alter K+ channel conductances. It has been suggested that the activities of K+ channels are responsible for the presynaptic modulation of neurotransmitter release from synaptosomes (Zoltay and Cooper, 1990). In addition, 12-lipoxygenase products act as presynaptic inhibitors of secretion by Aplysiu sensory neurons (Piomelli et al, 1987).…”

Presynaptic plasticity: The regulation of Ca2+-dependent transmitter release

“…It is unclear whether similar processes are relevant to the plasticity of the presynaptic nerve terminal. Studies on isolated nerve terminals (Tibbs et al, 1989;Zoltay and Cooper 1990;Barrie et al, 1991) and the squid giant axon (Robitaille and Charlton, 1992) indicate that modulation of presynaptic K + channels may be an important factor in the modulation of the presynaptic input-output relation. Phosphorylation of presynaptic K + channels may prolong presynaptic depolarizations upon incoming action potentials, and may thus lengthen the periods of Ca 2 + influx (presynaptic Ca 2 + channels involved in fast-acting transmitter secretion appear not to inactivate readily, McMahon and Nicholls, 1991) and potentiate transmitter release.…”