Verapamil, a Ca2+ entry blocker, targets the pore-forming subunit of cardiac type KATP channel (Kir6.2).

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Ninomiya T, Takano M, Haruna T, Kono Y, Horie M

Verapamil, a Ca2+ entry blocker, targets the pore-forming subunit of cardiac type KATP channel (Kir6.2).

J Cardiovasc Pharmacol. 2003 Aug;42(2):161-8. doi: 10.1097/00005344-200308000-00002.

PubMed ID

12883317 [ View in PubMed

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Abstract

This study investigated the mechanism by which verapamil, which blocks 10R1, l-type Ca2+ channel and the HERG channel, blocks ATP-sensitive K+ (K(ATP)) channels. In whole cell patch experiments, verapamil reversibly inhibited cardiac type K(ATP) (Kir6.2/SUR2A) channels previously activated by 100-micromol/L pinacidil. In inside-out patch experiments, verapamil inhibited the C-terminal truncated form of Kir6.2 (Kir6.2DeltaC36) in a concentration-dependent manner; half-maximal inhibition (IC(50)) was obtained at 11.5 +/- 2.8 micromol/L when Kir6.2DeltaC36 was expressed without SUR2A. Verapamil also inhibited Kir6.2/SUR2A with a similar potency; IC(50) was 8.9 +/- 2.1 micromol/L for Kir6.2/SUR2A (not statistically different from the value for Kir6.2DeltaC36 alone). Thus, verapamil appeared to target the pore-forming subunit Kir6.2 rather than SUR2A, a member of ABC superfamily. Verapamil did not decrease the single-channel conductance, but increased the closed time of Kir6.2/SUR2A. The mutations of Kir6.2DeltaC36 (Kir6.2DeltaC36-R50G, -K185Q, -G334D), which have much lower ATP sensitivity, had no significant effect on verapamil block, suggesting that the site at which verapamil mediates K(ATP) channel inhibition is not identical with that involved in ATP block.

DrugBank Data that Cites this Article

Drugs

Verapamil

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Verapamil	ATP-sensitive inward rectifier potassium channel 11	Protein	Humans	Unknown	Inhibitor	Details