Article date: December 2000
By: Stephen E Jones, Sergey Missan, Pavel Zhabyeyev, Terence F McDonald in Volume 131, Issue 8, pages 1809-1816
Previous studies on verapamil and D600 have established that the Ca2+‐channel blockers also inhibit delayed‐rectifier K+ currents in cardiac tissues and myocytes. However, estimated IC50 values range over two to three orders of concentration, and it is unclear whether this reflects a high selectivity by one or both of the phenylalkylamines for particular K+ channels. The purpose of the present study was to determine the concentration‐dependent actions of verapamil and D600 on three defined cardiac K+ currents.
Guinea‐pig ventricular myocytes in the conventional whole‐cell configuration were bathed with normal Tyrode's or K+‐free solution, and pulsed from −80 mV for measurement of the effects of 0.01 μM to 3 mM verapamil and D600 on the inwardly‐rectifying K+ current (IKl) and the two delayed‐rectifier K+ currents, rapidly‐activating IKr and slowly‐activating IKs.
The phenylalkylamines inhibited both inward‐ and outward‐directed IKl. The IC50 values for outward IKl were approximately 220 μM.
Verapamil and D600 were approximately equipotent inhibitors of the delayed‐rectifier K+ currents. They inhibited IKr with IC50 near 3 μM, and IKs with IC50 280 μM. These results are discussed in relation to previous findings on K+ currents and to the clinical actions of the drugs.
Previous studies on verapamil and D600 have established that the Ca2+‐channel blockers also inhibit delayed‐rectifier K+ currents in cardiac tissues and myocytes. However, estimated IC50 values range over two to three orders of concentration, and it is unclear whether this reflects a high selectivity by one or both of the phenylalkylamines for particular K+ channels. The purpose of the present study was to determine the concentration‐dependent actions of verapamil and D600 on three defined cardiac K+ currents.
Guinea‐pig ventricular myocytes in the conventional whole‐cell configuration were bathed with normal Tyrode's or K+‐free solution, and pulsed from −80 mV for measurement of the effects of 0.01 μM to 3 mM verapamil and D600 on the inwardly‐rectifying K+ current (IKl) and the two delayed‐rectifier K+ currents, rapidly‐activating IKr and slowly‐activating IKs.
The phenylalkylamines inhibited both inward‐ and outward‐directed IKl. The IC50 values for outward IKl were approximately 220 μM.
Verapamil and D600 were approximately equipotent inhibitors of the delayed‐rectifier K+ currents. They inhibited IKr with IC50 near 3 μM, and IKs with IC50 280 μM. These results are discussed in relation to previous findings on K+ currents and to the clinical actions of the drugs.
British Journal of Pharmacology (2000) 131, 1809–1816; doi:10.1038/sj.bjp.0703758
DOI: 10.1038/sj.bjp.0703758
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