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

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 h...

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Bibliographic Details
Published in:Drug design, development and therapy development and therapy, 2014-01, Vol.8 (default), p.2263-2271
Main Authors: Vonderlin, Nadine, Fischer, Fathima, Zitron, Edgar, Seyler, Claudia, Scherer, Daniel, Thomas, Dierk, Katus, Hugo A, Scholz, Eberhard P
Format: Article
Language:English
Subjects:
Anesthesia
Anesthesiology
anesthetics
Anesthetics - administration & dosage
Anesthetics - pharmacology
Benzodiazepines
Binding sites
Cardiac arrhythmia
Deactivation
Dependence
Electric Conductivity
Electric potential
Frequency dependence
Health aspects
Heart
HEK293 Cells
Humans
Inactivation
Inhibitors
Kv1.5 Potassium Channel - antagonists & inhibitors
Kv1.5 Potassium Channel - metabolism
Laboratory animals
Midazolam
Midazolam - administration & dosage
Midazolam - pharmacology
Mode of action
Oocytes
Open channels
Original Research
Pharmacology
Physiological aspects
Potassium
Potassium - metabolism
Potassium channels
Potassium channels (voltage-gated)
Side effects
Xenopus
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Description
Summary: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 I(Kur). 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.
ISSN:1177-8881
1177-8881
DOI:10.2147/dddt.s70461