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Rim1 modulates direct G-protein regulation of Cav2.2 channels

  • Ion Channels, Receptors and Transporters
  • Published:
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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 Ca2+ 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 Cav2.2 channels. Activation of μ-opioid receptors expressed in HEK-293 cells along with Cav2.2 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 Ca2+ 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 Ca2+ 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 Ca2+ channels by G-proteins.

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Author notes

  1. Norbert Weiss

    Present address: Department of Physiology and Pharmacology, Hotchkiss Brain Institute - University of Calgary, Calgary, Canada

Authors and Affiliations

  1. Laboratory of Ion Channels, Functions and Pathologies, Grenoble Institute of Neurosciences, Inserm U836, Grenoble, France

    Norbert Weiss & Michel De Waard

  2. Joseph Fourier University, Grenoble, France

    Norbert Weiss & Michel De Waard

  3. School of Medicine, FES Iztacala, National Autonomous University of Mexico (UNAM), Tlalnepantla, Mexico

    Alejandro Sandoval

  4. Department of Synthetic Chemistry and Biological Chemistry Kyoto University, Graduate School of Engineering, Kyoto University, Katsura Campus, Nishikyo-ku, Kyoto, Japan

    Shigeki Kyonaka & Yasuo Mori

  5. Department of Cell Biology CINVESTAV-IPN, Mexico City, Mexico

    Ricardo Felix

Authors
  1. Norbert Weiss
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  2. Alejandro Sandoval
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  3. Shigeki Kyonaka
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  4. Ricardo Felix
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  5. Yasuo Mori
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  6. Michel De Waard
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Correspondence to Norbert Weiss.

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Norbert Weiss and Alejandro Sandoval have contributed equally to this work

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Weiss, N., Sandoval, A., Kyonaka, S. et al. Rim1 modulates direct G-protein regulation of Cav2.2 channels. Pflugers Arch - Eur J Physiol 461, 447–459 (2011). https://doi.org/10.1007/s00424-011-0926-5

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  • DOI: https://doi.org/10.1007/s00424-011-0926-5

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