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Determinants of G Protein Inhibition of Presynaptic Calcium Channels

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Book cover Voltage-Gated Calcium Channels

Part of the book series: Molecular Biology Intelligence Unit ((MBIU))

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Summary

The modulation of presynaptic calcium channels following the activation of G-protein coupled receptors is a key regulatory mechanism of synaptic transmission. The past two decades have yielded a tremendous advance in our understanding of this phenomenon at the molecular level. It is now widely accepted that the closed conformation of the channel is stabilized upon binding of G protein βγ dimers directly to the cytoplasmic region linking domains I and II, and perhaps also to the C-terminus region, of the calcium channel α1 subunit. The channels consequently become reluctant to open, resulting in inhibition of current activity. The molecular mechanisms that control G protein regulation of calcium channels are immensely complex, as the extent of modulation depends on the membrane potential, Gβ subunit subtype, the presence of ancillary calcium channel subunits, PKC-dependent phosphorylation of the channel, RGS proteins, and on interactions with the presynaptic vesicle release protein complex. These intricate interactions between second messenger pathways, synaptic release proteins, calcium channels and G proteins allow for the potential of fine tuning the entry of calcium into the presynapse, and consequently, neurotransmitter release.

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  1. Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada

    Aparna Nirdosh & Gerald W. Zamponi Ph.D.

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Nirdosh, A., Zamponi, G.W. (2005). Determinants of G Protein Inhibition of Presynaptic Calcium Channels. In: Voltage-Gated Calcium Channels. Molecular Biology Intelligence Unit. Springer, Boston, MA. https://doi.org/10.1007/0-387-27526-6_9

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