KCNG4 Genetic Variant Linked to Migraine Prevents Expression of KCNB1

Author:

Lacroix Gabriel1,Bhat Shreyas123ORCID,Shafia Zerghona34,Blunck Rikard123ORCID

Affiliation:

1. Department of Physics, Université de Montréal, Montréal, QC H3T 1J4, Canada

2. Department of Pharmacology and Physiology, Université de Montréal, Montréal, QC H3T 1J4, Canada

3. Interdisciplinary Research Center on Brain and Learning (CIRCA), Université de Montréal, Montréal, QC H3T 1J4, Canada

4. Department of Neuroscience, Université de Montréal, Montréal, QC H3T 1J4, Canada

Abstract

Migraines are a common type of headache affecting around 15% of the population. The signalling pathways leading to migraines have not been fully understood, but neuronal voltage-gated ion channels, such as KCNG4, have been linked to this pathology. KCNG4 (Kv6.4) is a silent member of the superfamily of voltage-gated potassium (Kv) channels, which expresses in heterotetramers with members of the KCNB (Kv2) family. The genetic variant Kv6.4-L360P has previously been linked to migraines, but their mode of action remains unknown. Here, we characterized the molecular characteristics of Kv6.4-L360P when co-expressed with Kv2.1. We found that Kv6.4-L360P almost completely abolishes Kv2 currents, and we propose that this mechanism in the trigeminal system, linked to the initiation of migraine, leads to the pathology.

Funder

Canadian Institutes of Health Research

Natural Sciences and Engineering Research Council of Canada

Publisher

MDPI AG

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