Abstract
G-protein-mediated inhibition of Ca2+ current is ubiquitous in neurons, and in synaptic terminals it can lead to a reduction in transmitter release (presynaptic inhibition). This type of Ca2+ current inhibition can often be relieved by prepulse depolarization, so the disinhibition of Ca2+ current can combine with Ca2+-dependent mechanisms for activity-induced synaptic facilitation to amplify this form of short-term plasticity. We combine a mathematical model of a G-protein-regulated Ca2+ channel with a model of transmitter secretion to study the potential effects of G-protein-mediated Ca2+ channel inhibition and disinhibition on transmitter release and facilitation. We investigate several scenarios, with the goal of observing a range of behaviors that may occur in different synapses. We find that the effects of Ca2+ channel disinhibition depend greatly on the location and distribution of inhibited channels. Facilitation can be greatly enhanced if all channels are subject to inhibition or if the subpopulation of channels subject to inhibition are located closer to release sites than those insensitive to inhibition, an arrangement that has been suggested by recent experiments (Stanley and Mirotznik, 1997). We also find that the effect of disinhibition on facilitation is greater for longer action potentials. Finally, in the case of homosynaptic inhibition, where Ca2+ channel inhibition occurs through the binding of transmitter molecules to presynaptic autoreceptors, there will be little reduction in transmitter release during the first of two successive bursts of impulses. The reduction of release during the second burst will be significantly greater, and if the unbinding rate of autoreceptors is relatively low, then the effects of G-protein-mediated channel inhibition become more pronounced as the duration of the interburst interval is increased up to a critical point, beyond which the inhibitory effects become less pronounced. This is in contrast to presynaptic depression due to the depletion of the releasable vesicle pool, where longer interburst intervals allow for a more complete replenishment of the pool. Thus, G-protein-mediated Ca2+ current inhibition leads to a reduction in transmitter release, while having a highly variable amplifying effect on synaptic facilitation. The dynamic properties of this form of presynaptic inhibition are very different from those of vesicle depletion.
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Bertram, R., Behan, M. Implications of G-Protein-Mediated Ca2+ Channel Inhibition for Neurotransmitter Release and Facilitation. J Comput Neurosci 7, 197–211 (1999). https://doi.org/10.1023/A:1008976129832
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DOI: https://doi.org/10.1023/A:1008976129832