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 stiffness were measured in both Ca(2+)- and agonist-stimulated contractions of single isolated alpha-toxin-permeabilized smooth muscle cells. PKC function was inhibited with the pseudosubstrate inhibitor (residues 19-31) of PKC (PKI). For Ca2+ activation, PKI did not change (P > 0.05) steady-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), PKI 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 enhancement in alpha-toxin-permeabilized smooth muscle is due to the activation of PKC.
Brozovich
F V
FV
Department of Medicine, Case Western Reserve University, Cleveland, Ohio 44106-5038, USA.
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002199:Capillary Permeability; D006706:Homeostasis; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D011493:Protein Kinase C / Q000819:agonists* / Q000502:physiology*; D011817:Rabbits; D010738:Type C Phospholipases / Q000494:pharmacology*; D014661:Vasoconstriction / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D011493:Protein Kinase C; D010738:Type C Phospholipases; D002118:Calcium