Temperature and protein kinase C modulate myofilament Ca2+ sensitivity in pressurized rat cerebral arteries.
The effects of pharmacological activation and inhibition of protein kinase C (PKC) and temperature on the relationship between cytoplasmic Ca2+ and lumen diameter were studied in pressurized (50 mmHg) rat posterior cerebral arteries permeabilized with alpha-toxin. Increasing Ca2+ concentrations (30 nM-10 microM, 22 degrees 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 degrees 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 Ca2+ sensitization (e.g., EC50 at 5 microM = 126 nM) without changing efficacy. The effects of calphostin C, a PKC inhibitor, on Ca2+ sensitivity were minimal; however, the amplitude of Ca2+-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 Ca2+ sensitivity, and 2) changes in PKC activity can significantly alter both myofilament sensitivity to and constrictor efficacy of cytosolic Ca2+.
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Department of Obstetrics and Gynecology, The University of Vermont, College of Medicine, Burlington, Vermont 05405, USA.
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D008841:Actin Cytoskeleton / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000187:drug effects; D002536:Cerebral Arteries / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D003593:Cytoplasm / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D007769:Lactams / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009281:Naphthalenes / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D011921:Rats, Inbred WKY; D013696:Temperature; D010738:Type C Phospholipases / Q000494:pharmacology; D014661:Vasoconstriction
D007211:Indoles; D007769:Lactams; D009281:Naphthalenes; C043969:indolactam V; D011493:Protein Kinase C; D010738:Type C Phospholipases; C058819:calphostin C; D002118:Calcium