Effects of stimulation and inhibition of protein kinase C on the cytosolic calcium concentration in rabbit afferent arterioles

The effect of the protein kinase C (PKC) inhibitor chelerytrine (Ch) and the PKC activator 12-0-tetradecanoyl-phorbol-13-acetate (TPA) on the cytosolic calcium concentration ([Ca2+](i)) in isolated intact rabbit afferent arterioles was investigated. [Ca2+](i) was measured in the proximal and distal parts of the arteriole. Administration of 1 mu M Ch gave rise to a peak followed by an elevated level of [Ca2+](i) in both these parts. Neither the peal: nor the elevated level of [Ca2+](i) was significantly reduced by 1 mu M nifedipine. The relative peak increase in [Ca2+](i) in response to 1 mu M noradrenaline (NA) or to 10 nM angiotensin ii (All) was significantly blunted in both parts after preincubation with 1 mu M Ch. Depolarization with 25 mM K+ increased [Ca2+](i) in both parts. Preincubation with Ch did not affect the increase in [Ca2+](i) induced by 25 mM K+. TPA (10 and 100 nM) did not significantly affect the basal [Ca2+](i) in the afferent arteriole. The [Ca2+](i) response to NA or 25 mM K+ was not affected by TPA. We conclude that blockade of PKC, increases [Ca2+](i) in afferent arteriolar smooth muscle by a mechanism independent of L-type voltage-sensitive calcium channels. Inhibition of PKC blunts the relative increase in [Ca2+](i) in response to All and, to a lesser extent, that induced by NA. We conclude that PKC might be important in modulating the calcium changes that occur in response to these vasoconstrictors.