Trends in Neurosciences
Presynaptic nicotinic ACh receptors
Section snippets
Presynaptic and preterminal nACh receptors
Presynaptic receptors can be defined as receptors at or near the nerve terminal that can positively or negatively modulate transmitter release directly, or influence the probability of an action potential resulting in exocytosis. The concept of preterminal nACh receptors (Fig. 1) was raised by Wessler[12]to describe axonal receptors that modulate ACh release from motor-nerve terminals. Preterminal nACh receptors have also been defined on GABA-containing neurones in the rat interpeduncular
Heterogeneity of presynaptic nACh receptors
Given the diversity of nicotinic subunits expressed in neurones, one might reasonably enquire which subunit combinations constitute presynaptic nACh receptors, and if presynaptic nACh receptors show heterogeneity in different brain pathways or transmitter systems. The identification of subunits comprising native nACh receptors has been attempted by comparison with the characteristics of heterologously expressed combinations of subunits. However, this approach generally gives imperfect
Mechanism of action of presynaptic nACh receptors
Nicotinic ACh receptors positively modulate transmitter release. This is consistent with their operation as ligand-gated cation channels. Unlike metabotropic presynaptic receptors that only influence stimulated release, nACh receptors can elicit Ca2+-dependent transmitter release under resting conditions11, 54. This is explained readily by nACh-receptor activation resulting in Na+ influx and consequent depolarization, sufficient to activate local voltage-sensitive Ca2+ channels (VSCC). An
Physiological significance of presynaptic nACh receptors
A great many peripheral nerve endings, both sensory and motor, possess a variety of receptors, including nACh receptors, that in many instances seem to have no physiological relevance. That is to say, there is no evidence of how they might come into contact physiologically with their endogenous agonist. Why are they there? Perhaps because they do no harm, so that they have survived evolutionarily. Perhaps the local source of agonist, classical or novel, has not been discovered. In the CNS,
Note added in proof
The application of high-resolution techniques has disclosed presynaptic nicotinic modulation in the rat hippocampus. John Dani and colleagues[76]have reported that sub-micromolar concentrations of nicotine enhance glutamate-mediated neurotransmission in cultures of hippocampal neurones from postnatal rats. This effect was TTX-insensitive and blocked by the α7-selective antagonists αBgt or methyllycaconitine, favouring the participation of presynaptic α7-like nACh receptors. Similar observations
Acknowledgements
I am grateful to Paul Whiteaker and Bill Bowman for helpful discussions, and to Paul Clarke for his critical appraisal of this manuscript and for providing the data for Fig. 2A and Fig. 2B. Work in the author's laboratory is supported by grants from BBSRC, MRC, Wellcome Trust and BAT Co. Ltd.
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