Inactivation induced by pathogenic Ca<sub>v</sub>1.3 L‐type Ca<sup>2+</sup>‐channel variants enhances sensitivity for dihydropyridine Ca<sup>2+</sup> channel blockers
Mutations A749T and L271H induce pathogenic gating changes. Like wildtype, isradipine inhibition is strongly voltage-dependent. Our data explains their apparent higher drug sensitivity at a given negative voltage by the availability of more inactivated channels due to their more negative inactivation voltage range. Low nanomolar isradipine concentrations will only inhibit Ca<sub>v</sub>1.3 channels in neurons during prolonged depolarized states without selectivity for mutant channels.
Authors
- Ferenc Török (ORCID: https://orcid.org/0009-0006-8133-5778)
- Jan Matthes (ORCID: https://orcid.org/0000-0003-2754-1555)
- Monica L. Fernández‐Quintero (ORCID: https://orcid.org/0000-0002-6811-6283)
- Nadine J. Ortner (ORCID: https://orcid.org/0000-0003-3882-3283)
- Jörg Striessnig (ORCID: https://orcid.org/0000-0002-9406-7120)
- Sarah Salamon (ORCID: https://orcid.org/0009-0005-7435-405X)
Institutions
- University of Cologne (DE)
- Universität Innsbruck (AT)
Publication Details
- Journal
- British Journal of Pharmacology
- Published
- 2024-10-07
- DOI
- https://doi.org/10.1111/bph.17357
- Citations
- 3
- Primary Topic
- Cardiac electrophysiology and arrhythmias
- Type
- article
- Field-Weighted Citation Impact
- 1.21
Funders
- Austrian Science Fund