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Electrophysiological characterization of a CaV3.1 calcium channel mutation linked to trigeminal neuralgia

  • Ion Channels, Receptors and Transporters
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Abstract

Trigeminal neuralgia is a rare and debilitating disorder that affects one or more branches of the trigeminal nerve, leading to severe pain attacks and a poor quality of life. It has been reported that the CaV3.1 T-type calcium channel may play an important role in trigeminal pain and a recent study identified a new missense mutation in the CACNA1G gene that encodes the pore forming α1 subunit of the CaV3.1 calcium channel. The mutation leads to a substitution of an Arginine (R) by a Glutamine (Q) at position 706 in the I-II linker region of the channel. Here, we used whole-cell voltage-clamp recordings to evaluate the biophysical properties of CaV3.1 wild-type and R706Q mutant channels expressed in tsA-201 cells. Our data indicate an increase in current density in the R706Q mutant, leading to a gain-of-function effect, without changes in the voltage for half activation. Moreover, voltage clamp using an action potential waveform protocol revealed an increase in the tail current at the repolarization phase in the R706Q mutant. No changes were observed in the voltage-dependence of inactivation. However, the R706Q mutant displayed a faster recovery from inactivation. Hence, the gain-of-function effects in the R706Q CaV3.1 mutant have the propensity to impact pain transmission in the trigeminal system, consistent with a contribution to trigeminal neuralgia pathophysiology.

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Data availability

The data used in our study are available from the authors on reasonable request.

Abbreviations

TN:

Trigeminal neuralgia

WT:

Wild type

VGCCs:

Voltage-gated calcium channels

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Acknowledgements

We are grateful to Lina Chen for her technical support.

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Not applicable.

Funding

This work was supported by a Project Grant from the Canadian Institutes of Health Research (CIHR) to GWZ. EG held a Alberta Innovates Scholarship. GWZ is a Canada Research Chair.

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Authors and Affiliations

  1. Department of Clinical Neurosciences, Alberta Children’s Hospital Research Institute and Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Canada

    Abdulaziz M. Alaklabi, Eder Gambeta & Gerald W. Zamponi

  2. College of Medicine, Alfaisal University, Riyadh, Saudi Arabia

    Abdulaziz M. Alaklabi

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  1. Abdulaziz M. Alaklabi
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  2. Eder Gambeta
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  3. Gerald W. Zamponi
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Contributions

AMA and EG performed experiments and data analysis. EG designed the study and drafted the manuscript. GWZ supervised the study and co-wrote the manuscript. All authors read and approved the final manuscript.

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Correspondence to Eder Gambeta.

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Alaklabi, A.M., Gambeta, E. & Zamponi, G.W. Electrophysiological characterization of a CaV3.1 calcium channel mutation linked to trigeminal neuralgia. Pflugers Arch - Eur J Physiol 475, 711–718 (2023). https://doi.org/10.1007/s00424-023-02808-w

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