NA+- and K+-channels as molecular targets of the alkaloid ajmaline in skeletal muscle fibres.
Friedrich O, von Wegner F, Wink M, Fink R (2007)
Publication Language: English
Publication Status: Published
Publication Type: Journal article, Original article
Publication year: 2007
Journal
Publisher: Wiley-Blackwell
Book Volume: 151
Pages Range: 82-93
Journal Issue: 1
Open Access Link: http://onlinelibrary.wiley.com/doi/10.1038/sj.bjp.0707194/epdf
Abstract
BACKGROUND AND PURPOSE\nAjmaline is a widely used antiarrhythmic drug. Its action on voltage-gated ion channels in skeletal muscle is not well documented and we have here elucidated its effects on Na(+) and K(+) channels.\nEXPERIMENTAL APPROACH\nSodium (I(Na)) and potassium (I(K)) currents in amphibian skeletal muscle fibres were recorded using 'loose-patch' and two-microelectrode voltage clamp techniques (2-MVC). Action potentials were generated using current clamp.\nKEY RESULTS\nUnder 'loose patch' clamp conditions, the IC(50) for I(Na) was 23.2 microM with Hill-coefficient h=1.21. For I(K), IC(50) was 9.2 microM, h=0.87. Clinically relevant ajmaline concentrations (1-3 microM) reduced peak I(Na) by approximately 5% but outward I(K) values were reduced by approximately 20%. Na(+) channel steady-state activation and fast inactivation were concentration-dependently shifted towards hyperpolarized potentials ( approximately 10 mV at 25 microM). Inactivation curves were markedly flattened by ajmaline. Peak-I(K) under maintained depolarisation was reduced to approximately 30% of control values by 100 microM ajmaline. I(K) activation time constants were increased at least two-fold. Lower concentrations (10 or 25 microM) reduced steady-state-I(K) slightly but peak-I(K) significantly. Action potential generation threshold was increased by 10 microM ajmaline and repolarisation prolonged.\nCONCLUSIONS AND IMPLICATIONS\nAjmaline acts differentially on Na(+) and K(+) channels in skeletal muscle. This suggests at least multiple sites of action including the S4 subunit. Our data may provide a first insight into specific mechanisms of ajmaline-ion channel interaction in tissues other than cardiac muscle and could suggest possible side-effects that need to be further evaluated.
Authors with CRIS profile
Involved external institutions
Ruprecht-Karls-Universität Heidelberg
Germany (DE)
Goethe-Universität Frankfurt am Main
Germany (DE)
Germany (DE)
Goethe-Universität Frankfurt am Main
Germany (DE)
How to cite
APA:
Friedrich, O., von Wegner, F., Wink, M., & Fink, R. (2007). NA+- and K+-channels as molecular targets of the alkaloid ajmaline in skeletal muscle fibres. British Journal of Pharmacology, 151(1), 82-93. https://doi.org/10.1038/sj.bjp.0707194
MLA:
Friedrich, Oliver, et al. "NA+- and K+-channels as molecular targets of the alkaloid ajmaline in skeletal muscle fibres." British Journal of Pharmacology 151.1 (2007): 82-93.
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