PT  - JOURNAL ARTICLE
AU  - D Rampe
AU  - B Wible
AU  - D Fedida
AU  - R C Dage
AU  - A M Brown
TI  - Verapamil blocks a rapidly activating delayed rectifier K+ channel cloned from human heart.
DP  - 1993 Sep 01
TA  - Molecular Pharmacology
PG  - 642--648
VI  - 44
IP  - 3
4099  - http://molpharm.aspetjournals.org/content/44/3/642.short
4100  - http://molpharm.aspetjournals.org/content/44/3/642.full
SO  - Mol Pharmacol1993 Sep 01; 44
AB  - Verapamil is an antagonist of L-type Ca2+ channels, and part of its binding site is located in the sixth transmembrane segment (S6) in the fourth repeat of the protein. Verapamil also blocks K+ channels, which are members of the same supergene family as Ca2+ channels. We examined the effects of verapamil on a rapidly activating delayed rectifier K+ channel (designated fHK) cloned from human heart. Verapamil inhibited 86Rb+ efflux from fHK-transfected human embryonic kidney cells with an EC50 of 4.5 x 10(-5) M. Whole-cell patch-clamp experiments revealed that verapamil induced a rapid component of fHK current inactivation but was without effect on activation. The effect was concentration and voltage dependent and was attributed to open channel blockade. The apparent association and dissociation rate constants measured at +50 mV were about 1.65 x 10(5) M-1 sec-1 and 3.48 sec-1, respectively. S6 of fHK has significant homology to that portion of the verapamil binding site identified in Ca2+ channels, and S6 is thought to form part of the inner mouth of K+ channel pores. The data support a role for verapamil as a blocker of the inner pore of voltage-dependent K+ channels in human myocardium.