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Updated: Aug 6, 2026

Isolation and Kv Channel Recordings in Murine Atrial and Ventricular Cardiomyocytes
Published on: March 12, 2013
The acrylamide (S)-1 differentially affects Kv7 (KCNQ) potassium channels
Bo Hjorth Bentzen1, Nicole Schmitt, Kirstine Calloe
1The Danish National Research Foundation Centre for Cardiac Arrhythmia and Department of Medical Physiology, The Panum Institute, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark.
Abstract:
The family of Kv7 (KCNQ) potassium channels consists of five members. Kv7.2 and 3 are the primary molecular correlates of the M-current, but also Kv7.4 and Kv7.5 display M-current characteristics. M-channel modulators include blockers (e.g., linopirdine) for cognition enhancement and openers (e.g., retigabine) for treatment of epilepsy and neuropathic pain. We investigated the effect of a Bristol-Myers Squibb compound (S)-N-[1-(3-morpholin-4-yl-phenyl)-ethyl]-3-phenyl-acrylamide [(S)-1] on cloned human Kv7.1-5 potassium channels expressed in Xenopus laevis oocytes. Using two-electrode voltage-clamp recordings we found that (S)-1 blocks Kv7.1 and Kv7.1/KCNE1 currents. In contrast, (S)-1 produced a hyperpolarizing shift of the activation curve for Kv7.2, Kv7.2/Kv7.3, Kv7.4 and Kv7.5. Further, the compound enhanced the maximal current amplitude at all potentials for Kv7.4 and Kv7.5 whereas the combined activation/block of Kv7.2 and Kv7.2/3 was strongly voltage-dependent. The tryptophan residue 242 in S5, known to be crucial for the effect of retigabine, was also shown to be critical for the enhancing effect of (S)-1 and BMS204352. Furthermore, no additive effect on Kv7.4 current amplitude was observed when both retigabine and (S)-1 or BMS204352 were applied simultaneously. In conclusion, (S)-1 differentially affects the Kv7 channel subtypes and is dependent on a single tryptophan for the current enhancing effect in Kv7.4.
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