Ha. Desilva et al., PHARMACOLOGICAL EVIDENCE OF CALCIUM-ACTIVATED AND VOLTAGE-GATED POTASSIUM CHANNELS IN HUMAN PLATELETS, Clinical science, 93(3), 1997, pp. 249-255
1. Previous electrophysiological studies have suggested the presence o
f K-Ca and K-v channels in human platelets, However, the pharmacology
of these channels has not been defined. 2. We have studied potassium c
hannels in human platelets by measuring the efflux of Rb-86(+) (a mark
er for K+) from Rb-86(+)-loaded cells, and have defined their response
s to stimulation by the platelet agonist thrombin and the calcium iono
phore ionomycin. 3. Thrombin stimulated an increase in Rb-86(+) efflux
from the platelets in a concentration-dependent manner. This efflux w
as significantly inhibited by apamin (100 nmol/l), charybdotoxin (300
nmol/l) and alpha-dendrotoxin (100-200 nmol/l), blockers of SKCa chann
els, K-Ch channels and K-v channels respectively. Iberiotoxin (300 nmo
l/l), a specific inhibitor of BKCa channels, had no effect on the thro
mbin-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 c
oncentration-dependent manner, This efflux was significantly inhibited
by apamin (100 nmol/l) and charybdotoxin (300 nmol/l). However, iberi
otoxin (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 cha
nnel: SKCa and K-Ch channels. Thrombin also stimulated efflux via K-v
channels.