Effects of calcium channel blockers on cloned cardiac K+ channels IKr and IKs.

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Chouabe C, Drici MD, Romey G, Barhanin J

Effects of calcium channel blockers on cloned cardiac K+ channels IKr and IKs.

Therapie. 2000 Jan-Feb;55(1):195-202.

PubMed ID

10860024 [ View in PubMed

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Abstract

Cloned HERG and KvLQT1-IsK K+ channels have been expressed in mammalian cells and assayed as a target for calcium channel blockers. These channels generate the rapid and slow components of the cardiac delayed rectifier K+ current, and mutations can affect them that lead to long QT syndromes. HERG is blocked by bepridil (EC50 = 0.55 microM), verapamil (EC50 = 0.83 microM) and mibefradil (EC50 = 1.43 microM), whereas nitrendipine and diltiazem have negligible effects. Steady-state activation and inactivation parameters are shifted to more negative values in the presence of the blockers. Similarly, KvLQT1-IsK is inhibited by bepridil (EC50 = 10.0 microM) and mibefradil (EC50 = 11.8 microM), whilst being insensitive to nitrendipine, diltiazem or verapamil. This work may help to understand the mechanisms of action of verapamil in certain ventricular tachycardias as well as some of the deleterious adverse cardiac events associated with bepridil and mibefradil.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Bepridil	Potassium voltage-gated channel subfamily KQT member 1	Protein	Humans	Unknown	Inhibitor	Details