20‐Hydroxyeicosatetraenoic acid potentiates stretch‐induced contraction of canine basilar artery <i>via</i> PKCα‐mediated inhibition of K_Ca channel

Abstract

1. The present study was undertaken to elucidate whether PKCalpha 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 PKCalpha 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 PKCalpha-mediated inhibition of K(Ca) channel activity.