Regulation of Ca 2+ sensitization by PKC and rho proteins in ovine cerebral arteries: effects of artery size and age

• Published in: American journal of physiology. Heart and circulatory physiology 1998-09, Vol.275 (3), p.H930-H939
• Main Authors: Akopov, Sergey E, Zhang, Lubo, Pearce, William J
• Format: Article
• Language: English
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.1998.275.3.H930

G protein-regulated Ca sensitivity of vascular contractile proteins plays an important role in cerebrovascular reactivity. The present study examines the intracellular mechanisms that govern G protein-regulated Ca sensitivity in cerebral arteries of different size and age. We studied β-escin-permeabilized segments of common carotid, basilar, and middle cerebral arteries from nonpregnant adult and near-term fetal sheep. Activation of protein kinase C (PKC) by (-)-indolactam V or a phorbol ester produced receptor-independent increases in Ca sensitivity. Such increases were more marked in immature arteries and were inversely correlated with artery size in both mature and immature arteries. However, inhibitors of PKC did not significantly affect increases in Ca sensitivity in responses to either serotonin (5-hydroxytryptamine, 5-HT) or guanosine 5'- O-(3-thiotriphosphate) (GTPγS). Alternatively, deactivation of rho p21, a small G protein associated with Rho kinase, by exotoxin C3 fully prevented increases in Ca sensitivity in responses to 5-HT or GTPγS in both adult and fetal arteries of all types. Neither inhibitors of PKC nor exotoxin C3 altered baseline Ca sensitivity. We conclude that patterns of receptor- and/or G protein-mediated modulation of Ca sensitivity are dependent on an intracellular pathway that involves activation of small G proteins and Rho kinase. In contrast, PKC has little, if any, role in agonist-induced Ca sensitization under the present experimental conditions.