Sensitivity to protein kinase C inhibitors of nicardipine‐insensitive component of high K+ contracture in rat and guinea‐pig aorta

1. In the rat and guinea-pig aorta, we observed that the contraction to hypertonically-added K+, unlike the isotonic K(+)-induced contraction, was only partially sensitive to nicardipine (0.1, 1 and 10 microM), an L-type Ca2+ channel blocker and occurred in Ca(2+)-free medium containing 50 microM EGTA. We have characterized this nicardipine-insensitive hypertonically-added K+ contraction. 2. The contraction induced by an equi-osmolar concentration of mannitol was similar in size to that evoked by hypertonically-added K+. 3. When the tissue was depleted of its internal Ca2+ stores with various agents such as phenylephrine (10 microM) cyclopiazonic acid (30 microM), thapsigargin (1 microM) or ryanodine (30 microM), or by incubation in Ca(2+)-free medium over 30 min, little effect was observed on the high K+ contracture in the presence of L-type Ca2+ channel blockade. 4. Phentolamine (10 microM) or indomethacin (10 microM) did not reduce the contraction induced by high K+. 5. Application of a protein kinase C inhibitor, H7 (10, 30 and 100 microM) or calphostin C (1 microM), reduced the high K+ contraction but not that caused by an equi-osmolar concentration of mannitol. 6. The data suggest that hypertonic K(+)-induced contraction differs from that caused by hypertonicity or depolarization per se and invokes membrane enzyme activation.