Cytochalasin inhibition of slow tension increase in rat aortic rings.
We separated the K(+)-induced contraction of rat aortic rings into its initial (fast) and secondary (slow) components. It was found that temperature sensitivity, K+ depolarization, and Ca2+ dependency could each be utilized to differentiate between these two components of the contractile response. Increasing the passive tension preload of the tissue increased the fast response but had no significant effect on the secondary slow rise in tension. Cytochalasins, which inhibit actin polymerization, reversibly inhibited tension development by rat aortic rings with the effect selectively confined to the slow component of the K(+)-induced contraction. In a similar fashion, cytochalasin was shown to attenuate the slow tension increase caused by phorbol 12,13-dibutyrate. Finally, it was found that low concentrations of the protein kinase C (PKC) inhibitor staurosporine (8 x 10(-9) M) selectively attenuated the slow component of the K(+)-induced contraction. The results suggest that distinctly different mechanisms regulate the initial fast and secondary slow contractile responses induced by elevation of extracellular K+. Both mechanisms are voltage sensitive and use extracellular Ca2+. The fast but not the slow component was altered by changing the passive tension preload in a fashion consistent with a sliding filament mechanism of force development. The specific nature of the slow component is not certain but may involve low-level PKC activity and require the integrity and capability for remodeling of a specific portion of the actin-containing cytoskeleton.
Wright
G
G
Department of Physiology, Marshall University School of Medicine, Huntington, West Virginia 25755.
Hurn
E
E
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology*; D003571:Cytochalasin B / Q000494:pharmacology*; D003572:Cytochalasins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D019311:Staurosporine; D013696:Temperature
D000470:Alkaloids; D003572:Cytochalasins; C031218:cytochalasin A; D015240:Phorbol 12,13-Dibutyrate; D003571:Cytochalasin B; D011189:Potassium Chloride; D011493:Protein Kinase C; D019311:Staurosporine