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

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

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