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 ⁸⁶Rb⁺ (a marker for K⁺) from ⁸⁶Rb⁺-loaded cells, and have defined their responses to stimulation by the platelet agonist thrombin and the calcium ionophore ionomycin.

3. Thrombin (0.1–0.6 i.u./ml) stimulated an increase in ⁸⁶Rb⁺ efflux from the platelets in a concentration-dependent manner. This efflux was significantly inhibited by apamin (100 nmol/l), charybdotoxin (300 nmol/l) and α-dendrotoxin (100–200 nmol/l), blockers of SK_Ca channels, K_Ch channels and K_v channels respectively. Iberiotoxin (300 nmol/l), a specific inhibitor of BK_Ca channels, had no effect on the thrombin-stimulated ⁸⁶Rb⁺ efflux. Although glibenclamide, an inhibitor of K_ATP channels, inhibited the thrombin-stimulated efflux, it did so only in a high concentration (20 μmol/l).

4. Ionomycin (1–5 μmol/l) stimulated an increase in ⁸⁶Rb⁺ 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 ⁸⁶Rb⁺ efflux.

5. These findings suggest that ⁸⁶Rb⁺ efflux from platelets stimulated by thrombin and ionomycin occurs via two types of K_Ca channel: SK_Ca and K_Ch channels. Thrombin also stimulated efflux via K_v channels.