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Rim1 modulates direct G-protein regulation of Ca(v)2.2 channels.

Abstract : Regulation of presynaptic voltage-gated calcium channels is critical for depolarization-evoked neurotransmitter release. Various studies attempted to determine the functional implication of Rim1, a component of the vesicle release machinery. Besides to couple voltage-gated Ca(2+) channels to the presynaptic vesicle release machinery, it was evidenced that Rim1 also prevents voltage-dependent inactivation of the channels through a direct interaction with the ancillary β-subunits, thus facilitating neurotransmitter release. However, facilitation of synaptic activity may also be caused by a reduction of the inhibitory pathway carried by G-protein-coupled receptors. Here, we explored the functional implication of Rim1 in G-protein regulation of Ca(v)2.2 channels. Activation of μ-opioid receptors expressed in HEK-293 cells along with Ca(v)2.2 channels produced a drastic current inhibition both in control and Rim1-expressing cells. In contrast, Rim1 considerably promoted the extent of current deinhibition following channel activation, favoring sustained Ca(2+) influx under prolonged activity. Our data suggest that Rim1-induced facilitation of neurotransmitter release may come as a consequence of a decrease in the inhibitory pathway carried by G-proteins that contributes, together with the slowing of channel inactivation, to maintain Ca(2+) influx under prolonged activity. The present study also furthers functional insights in the importance of proteins from the presynaptic vesicle complex in the regulation of voltage-gated Ca(2+) channels by G-proteins.
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Submitted on : Wednesday, April 20, 2011 - 5:15:44 PM
Last modification on : Thursday, May 20, 2021 - 4:50:02 PM
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Norbert Weiss, Alejandro Sandoval, Shigeki Kyonaka, Ricardo Felix, yasuo Mori, et al.. Rim1 modulates direct G-protein regulation of Ca(v)2.2 channels.. Pflügers Archiv European Journal of Physiology, Springer Verlag, 2011, 461 (4), pp.447-59. ⟨10.1007/s00424-011-0926-5⟩. ⟨inserm-00587552⟩



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