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Determinants of G protein inhibition of presynaptic calcium channels

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Abstract

The modulation of presynaptic calcium (Ca) channels by heterotrimeric G proteins is a key factor for the regulation of neurotransmission. Over the past 20 yr, a significant understanding of the molecular events underlying this regulation has been acquired. It is now widely accepted that binding of G protein βγ dimers directly to the cytoplasmic region linking domains I and II of the Ca channel α1 subunit results in a stabilization of the closed conformation of the channel, thereby inhibiting current activity. The extent of the inhibition is dependent on the Gβ subunit isoform, and is antagonized by both strong membrane depolarizations and protein kinase C-dependent phosphorylation of the channel. Finally, the inhibition is critically modulated by regulator of G protein signaling proteins, and by proteins forming the presynaptic vesicle release complex. Thus, the regulation of the activities of presynaptic Ca channels is becoming increasingly complex, a feature that may contribute to the overall fine-tuning of Ca entry into presynaptic nerve termini, and thus, neurotransmission.

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  1. Departments of Physiology and Biophysics, and Pharmacology and Therapeutics, Neuroscience Research Group, University of Calgary, T2N 4N1, Calgary, Canada

    Gerald W. Zamponi

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Zamponi, G.W. Determinants of G protein inhibition of presynaptic calcium channels. Cell Biochem Biophys 34, 79–94 (2001). https://doi.org/10.1385/CBB:34:1:79

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