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

The present study was undertaken to elucidate whether PKCα 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. Slow stretch at rates of 0.1 to 3 mm s −1 did not produce any contraction in normal physiological solution. 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. 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. Calphostin C, an inhibitor of protein kinase C (PKC), inhibited the action of 20‐HETE, but not that of iberiotoxin. In response to 20‐HETE PKCα isoform was translocated from the cytosol to the membrane fraction, which translocation was inhibited by calphostin C. 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. British Journal of Pharmacology (2002) 137 , 1362–1370. doi: 10.1038/sj.bjp.0704960