Drugs acting at TRPM7 channels inhibit seizure-like activity

Aytakin Khalil; Tawfeeq Shekh-Ahmad; Stjepana Kovac; Robert C. Wykes; F. David Horgen; Andrea Fleig; Matthew C. Walker

doi:10.1002/epi4.12773

Drugs acting at TRPM7 channels inhibit seizure-like activity

Aytakin Khalil, Tawfeeq Shekh-Ahmad, Stjepana Kovac, Robert C. Wykes, F. David Horgen, Andrea Fleig, Matthew C. Walker^*

^*Corresponding author for this work

School of Pharmacy

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

Transient receptor potential cation subfamily M7 (TRPM7) channels are ion channels permeable to divalent cations. They are abundantly expressed with particularly high expression in the brain. Previous studies have highlighted the importance of TRPM7 channels in brain diseases such as stroke and traumatic brain injury, yet evidence for a role in seizures and epilepsy is lacking. Here, we show that carvacrol, a food additive that inhibits TRPM7 channels, and waixenicin A, a novel selective and potent TRPM7 inhibitor, completely suppressed seizure-like activity in rodent hippocampal-entorhinal brain slices exposed to pentylenetetrazole or low magnesium. These findings support inhibition of TRPM7 channels as a novel target for antiseizure medications.

Original language	English
Pages (from-to)	1169-1174
Number of pages	6
Journal	Epilepsia Open
Volume	8
Issue number	3
DOIs	https://doi.org/10.1002/epi4.12773
State	Published - Sep 2023

Bibliographical note

Publisher Copyright:
© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.

Keywords

TRPM7
carvacrol
epilepsy
seizure
waixenicin A

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/epi4.12773

Cite this

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title = "Drugs acting at TRPM7 channels inhibit seizure-like activity",

abstract = "Transient receptor potential cation subfamily M7 (TRPM7) channels are ion channels permeable to divalent cations. They are abundantly expressed with particularly high expression in the brain. Previous studies have highlighted the importance of TRPM7 channels in brain diseases such as stroke and traumatic brain injury, yet evidence for a role in seizures and epilepsy is lacking. Here, we show that carvacrol, a food additive that inhibits TRPM7 channels, and waixenicin A, a novel selective and potent TRPM7 inhibitor, completely suppressed seizure-like activity in rodent hippocampal-entorhinal brain slices exposed to pentylenetetrazole or low magnesium. These findings support inhibition of TRPM7 channels as a novel target for antiseizure medications.",

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AU - Shekh-Ahmad, Tawfeeq

AU - Kovac, Stjepana

AU - Wykes, Robert C.

AU - Horgen, F. David

AU - Fleig, Andrea

AU - Walker, Matthew C.

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AB - Transient receptor potential cation subfamily M7 (TRPM7) channels are ion channels permeable to divalent cations. They are abundantly expressed with particularly high expression in the brain. Previous studies have highlighted the importance of TRPM7 channels in brain diseases such as stroke and traumatic brain injury, yet evidence for a role in seizures and epilepsy is lacking. Here, we show that carvacrol, a food additive that inhibits TRPM7 channels, and waixenicin A, a novel selective and potent TRPM7 inhibitor, completely suppressed seizure-like activity in rodent hippocampal-entorhinal brain slices exposed to pentylenetetrazole or low magnesium. These findings support inhibition of TRPM7 channels as a novel target for antiseizure medications.

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Drugs acting at TRPM7 channels inhibit seizure-like activity

Abstract

Bibliographical note

Keywords

UN SDGs

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