20-Hydroxyeicosatetraenoic acid potentiates stretch-induced contraction of canine basilar artery via PKCα-mediated inhibition of K ca channel

Abstract

1. The present study was undertaken to elucidate whether PK Cα plays a role in the mechanism of the stretch-induced contraction potentiated by 20-hydroxyeicosatetraenoic acid (20-HETE). The effects of 20-HETE on the canine basilar artery were compared with those of iberiotoxin, a blocker of large conductance Ca 2+-activated K + channels (K Ca channels), as this blocker was shown earlier to sensitize these arteries to mechanical stretch. 2. Slow stretch at rates of 0.1 to 3 mm s -1 did not produce any contraction in normal physiological solution. 3. In the presence of 20-HETE, the slow stretch could produce contraction, which was inhibited by nicardipine, a 1,4-dihydropyridine Ca 2+ channel blocker, and gadolinium, a blocker of stretch-activated cation channels. 4. 20-HETE inhibited whole-cell K + current and depolarized the membrane by approximately 10 mV. These effects of 20-HETE were similar to those of iberiotoxin. 5. Calphostin C, an inhibitor of protein kinase C (PKC), inhibited the action of 20-HETE, but not that of iberiotoxin. 6. In response to 20-HETE PKCα isoform was translocated from the cytosol to the membrane fraction, which translocation was inhibited by calphostin C. 7. These results suggest that 20-HETE induced sensitization of the canine basilar artery to stretch was caused by PKCα-mediated inhibition of K Ca channel activity.