EFFECTS OF STIMULATION AND INHIBITION OF PROTEIN-KINASE-C ON THE CYTOSOLIC CALCIUM-CONCENTRATION IN RABBIT AFFERENT ARTERIOLES

The effect oi the protein kinase C (PKC) inhibitor chelerytrine (Ch) a nd the PKC activator 12-0-tetradecanoyl-phorbol-13-acetate (TPA) on th e cytosolic calcium concentration ([Ca2+](i)) in isolated intact rabbi t afferent arterioles was investigated. [Ca2+](i) was measured in the proximal and distal parts oi the arteriole. Administration of 1 mu M C h gave rise to a peak followed by an elevated level of [Ca2+](i) in bo th these parts. Neither the peal: nor the elevated level of [Ca2+](i) was significantly reduced by 1 mu M nifedipine. The relative peak incr ease 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 pr eincubation with 1 mu M Ch. Depolarization with 25 mM K+ increased [Ca 2+](i) in both parts. Preincubation with Ch did not affect the increas e in [Ca2+](i) induced by 25 mM K+. TPA (10 and 100 nM) did not signif icantly 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 smoot h muscle by a mechanism independent of L-type voltage-sensitive calciu m 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 c onclude that PKC might be important in modulating the calcium changes that occur in response to these vasoconstrictors.