Abstract
The compound BMS-204352 has been targeted for use against acute ischemic stroke, due to its activation of the large-conductance Ca2+-activated K-channel (BK). We have previously described that the racemate (±)BMS-204352 reversibly modulates KCNQ4 voltage dependency. Here we show that (±)BMS-204352 also induces a voltage-independent KCNQ4 current. The channels were stably expressed in human embryonic kidney cells (HEK293), and investigated by use of the whole-cell mode of the patch-clamp technique. (±)BMS-204352 was applied extracellularly (10 μM) in order to precipitate the robust appearance of the voltage-independent current. The voltage-independent KCNQ4 currents were recorded as instantaneous increases in currents upon hyperpolarizing or depolarizing voltage steps elicited from holding potentials of –90 or −110 mV. The voltage-independent current reversed at the equilibrium potential for potassium (E K), hence was carried by a K+ conductance, and was blocked by the selective KCNQ channel blockers XE991 and linopirdine. Similar results were obtained with KCNQ4 channels transiently transfected into Chinese hamster ovary cells (CHO). When (±)BMS-204352 was applied to stably expressed BK channels, only the voltage dependency was modulated. Retigabine, the classic activator of KCNQ channels, did not induce voltage-independent currents. Our data indicate that KCNQ4 channels may conduct voltage-dependent and voltage-independent currents in the presence of (±)BMS-204352.
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The Danish Heart Association supported the work.
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Schrøder, R.L., Strøbaek, D., Olesen, SP. et al. Voltage-independent KCNQ4 currents induced by (±)BMS-204352. Pflugers Arch - Eur J Physiol 446, 607–616 (2003). https://doi.org/10.1007/s00424-003-1116-x
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DOI: https://doi.org/10.1007/s00424-003-1116-x