Pharmacological evidence of calcium-activated and voltage-gated potassium channels in human platelets

1. Previous electrophysiological studies have suggested the presence of K-Ca and K-v channels in human platelets, However, the pharmacology of these channels has not been defined. 2. We have studied potassium channels in human platelets by measuring the efflux of Rb-86(+) (a marker for K+) from Rb-86(+)-loaded cells, and have defined their responses to stimulation by the platelet agonist thrombin and the calcium ionophore ionomycin. 3. Thrombin stimulated an increase in Rb-86(+) efflux from the platelets in a concentration-dependent manner. This efflux was significantly inhibited by apamin (100 nmol/l), charybdotoxin (300 nmol/l) and alpha-dendrotoxin (100-200 nmol/l), blockers of SKCa channels, K-Ch channels and K-v channels respectively. Iberiotoxin (300 nmol/l), a specific inhibitor of BKCa channels, had no effect on the thrombin-stimulated Rb-86(+) efflux. Although glibenclamide, an inhibitor of K-ATP channels, inhibited the thrombin-stimulated efflux, it did so only in a high concentration (20 mu mol/l). 4. Ionomycin (1-5 mu mol/l) stimulated an increase in Rb-86(+) efflux from the platelets in a concentration-dependent manner, This efflux was significantly inhibited by apamin (100 nmol/l) and charybdotoxin (300 nmol/l). However, iberiotoxin (300 nmol/l) had no effect on the ionomycin-stimulated Rb-86(+) efflux. 5. These findings suggest that Rb-86(+) efflux from platelets stimulated by thrombin and ionomycin occurs via two types of K-Ca channel: SKCa and K-Ch channels. Thrombin also stimulated efflux via K-v channels.