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Inhibition of cardiac Kv1.5 potassium current by the anesthetic midazolam: mode of action

Authors Vonderlin N, Fischer F, Zitron E, Seyler C, Scherer D, Thomas D, Katus HA, Scholz E

Received 1 July 2014

Accepted for publication 31 July 2014

Published 7 November 2014 Volume 2014:8 Pages 2263—2271

DOI https://doi.org/10.2147/DDDT.S70461

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Editor who approved publication: Professor Shu-Feng Zhou

Nadine Vonderlin,1 Fathima Fischer,1 Edgar Zitron,1,2 Claudia Seyler,1 Daniel Scherer,1 Dierk Thomas,1,2 Hugo A Katus,1,2 Eberhard P Scholz1

1Department of Internal Medicine III, University Hospital Heidelberg, Heidelberg, Germany; 2German Centre for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, Heidelberg, Germany

Abstract: Midazolam is a short-acting benzodiazepine that is widely used in anesthesia. Despite its widespread clinical use, detailed information about cardiac side effects of midazolam is largely lacking. Using the double-electrode voltage clamp technique, we studied pharmacological effects of midazolam on heterologously expressed Kv1.5 channels underlying atrial repolarizing current IKur. Midazolam dose-dependently inhibited Kv1.5 current, yielding an IC50 of 17 µM in an HEK cell line and an IC50 of 104 µM in Xenopus oocytes. We further showed that midazolam did not affect the half-maximal activation voltage of Kv1.5 channels. However, a small negative shift of the inactivation curve could be observed. Midazolam acted as a typical open-channel inhibitor with rapid onset of block and without frequency dependence of block. Taken together, midazolam is an open channel inhibitor of cardiac Kv1.5 channels. These data add to the current understanding of the pharmacological profile of midazolam.

Keywords: anesthetics, potassium channels, pharmacology

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