Abstract
THE most commonly used signal transduction pathway for receptor-mediated N-type Ca2+-channel modulation involves activation of a heterotrimeric G protein to produce voltage-dependent inhibition1. Although it is widely assumed that Gα mediates this effect, experiments to address this hypothesis directly are lacking. Here I show that transient overexpression of Gβγ in sympathetic neurons mimics and occludes the voltage-dependent Ca2+ channel modulation produced by noradrenaline (NA). Conversely, over-expression of Gα produces minimal effects on basal Ca2+ channel behaviour but attenuates NA-mediated inhibition in a manner consistent with the buffering of Gβγ. These observations indicate that it is Gβγ, and not Gα, that mediates voltage-dependent inhibition of N-type Ca2+ channels. The identification of Gβγ as the mediator of this pathway has broad implications as G-protein-coupled receptors, many of which are implicated in disease or are targets of therapeutic agents, couple to N-type Ca2+ channels2 and may modulate synaptic transmission by this mechanism3,4.
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Ikeda, S. Voltage-dependent modulation of N-type calcium channels by G-protein β γsubunits. Nature 380, 255–258 (1996). https://doi.org/10.1038/380255a0
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DOI: https://doi.org/10.1038/380255a0
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