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Opioid Receptor Regulation of Neuronal Voltage-Gated Calcium Channels

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Abstract

Neuronal voltage-gated calcium channels play a pivotal role in the conversion of electrical signals into calcium entry into nerve endings that is required for the release of neurotransmitters. They are under the control of a number of cellular signaling pathways that serve to fine tune synaptic activities, including G-protein coupled receptors (GPCRs) and the opioid system. Besides modulating channel activity via activation of second messengers, GPCRs also physically associate with calcium channels to regulate their function and expression at the plasma membrane. In this mini review, we discuss the mechanisms by which calcium channels are regulated by classical opioid and nociceptin receptors. We highlight the importance of this regulation in the control of neuronal functions and their implication in the development of disease conditions. Finally, we present recent literature concerning the use of novel μ-opioid receptor/nociceptin receptor modulators and discuss their use as potential drug candidates for the treatment of pain.

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Abbreviations

VGCC:

Voltage-gated calcium channel

OR:

Opioid receptor

MOR:

Mu opioid receptor

DOR:

Delta opioid receptor

KOR:

Kappa opioid receptor

NOP:

Nociceptin receptor

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Funding

NW is supported by the Institute of Organic Chemistry and Biochemistry. GWZ is supported by a grant from the Canadian Institutes for Health Research and holds a Canada Research Chair.

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  1. Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czech Republic

    Norbert Weiss

  2. Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic

    Norbert Weiss

  3. Department of Physiology and Pharmacology, Hotchkiss Brain Institute and Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Canada

    Gerald W. Zamponi

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NW and GWZ reviewed the literature and wrote the manuscript.

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Weiss, N., Zamponi, G.W. Opioid Receptor Regulation of Neuronal Voltage-Gated Calcium Channels. Cell Mol Neurobiol 41, 839–847 (2021). https://doi.org/10.1007/s10571-020-00894-3

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