PKC REGULATES AGONIST-INDUCED FORCE ENHANCEMENT IN SINGLE ALPHA-TOXIN-PERMEABILIZED VASCULAR SMOOTH-MUSCLE CELLS

To determine whether activation of protein kinase C (PKC) is involved in the mechanism of agonist-induced force enhancement, force and stiff ness were measured in both Ca2+- and agonist-stimulated contractions o f single isolated alpha-toxin-permeabilized smooth muscle cells. PKC f unction was inhibited with the pseudosubstrate inhibitor (residues 19- 31) of PKC (PKI). For Ca2+ activation, PKI did not change (P > 0.05) s teady-state force or stiffness. However, for agonist activation at pCa 7 (n = 13), PKI depressed force by 28.7 +/- 4.5% (P < 0.05), in-phase stiffness by 35.4 +/- 4.0% (P < 0.05), and quadrature stiffness by 25 .6 +/- 4.4% (P < 0.05), and for agonist activation at pCa 4 (n = 7), P KI depressed force by 25.8 +/- 2.9% (P < 0.05), in-phase stiffness by 35.6 +/- 5.6% (P < 0.05), and quadrature stiffness by 20.3 +/- 4.1% (P < 0.05). These results suggest that the agonist-induced force enhance ment in alpha-toxin-permeabilized smooth muscle is due to the activati on of PKC.