Temperature and protein kinase C modulate myofilament Ca21 sensitivity in pressurized rat cerebral arteries

Gokina, Natalia I., and George Osol. Temperature and protein kinase C modulate myofilament Ca21 sensitivity in pressurized rat cerebral arteries. Am. J. Physiol. 274 (Heart Circ. Physiol. 43): H1920–H1927, 1998.—The effects of pharmacological activation and inhibition of protein kinase C (PKC) and temperature on the relationship between cytoplasmic Ca21 and lumen diameter were studied in pressurized (50 mmHg) rat posterior cerebral arteries permeabilized with a-toxin. Increasing Ca21 concentrations (30 nM–10 μM, 22°C) induced stable, concentration-dependent constrictions with a half-maximal effective concentration (EC50) of 112 nM. The maximal constriction was 80% of baseline diameter and 157% of that during depolarization of nonpermeabilized vessels with 124 mM KCl. Elevation of temperature to 37°C increased the EC50 to 246 nM and enhanced the steepness of concentration-response curves. Exposure of permeabilized arteries to indolactam V, an activator of PKC, resulted in a significant myofilament Ca21 sensitization (e.g., EC50 at 5 μM 5 126 nM) without changing efficacy. The effects of calphostin C, a PKC inhibitor, on Ca21 sensitivity were minimal; however, the amplitude of Ca21-induced constrictions in both control and indolactam-treated arteries was suppressed in a concentration-dependent manner. Thus 1) temperature is an important variable in studies of arterial Ca21 sensitivity, and 2) changes in PKC activity can significantly alter both myofilament sensitivity to and constrictor efficacy of cytosolic Ca21.