CYTOCHALASIN INHIBITION OF SLOW TENSION INCREASE IN RAT AORTIC RINGS

We separated the K+-induced contraction of rat aortic;rings into its i nitial (fast) and secondary (slow) components. It was found that tempe rature sensitivity, K+ depolarization, and Ca2+ dependency could each be utilized to differentiate between these two components of the contr actile response. Increasing the passive tension preload of the tissue increased the fast response but had no significant effect on the secon dary slow rise in tension. Cytochalasins, which inhibit actin polymeri zation, reversibly inhibited tension development by rat aortic rings w ith the effect selectively confined to the slow component of the K+-in duced contraction. In a similar fashion, cytochalasin was shown to att enuate the slow tension increase caused by phorbol 12,13-dibutyrate. F inally, 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 tha t distinctly different mechanisms regulate the initial fast and second ary slow contractile responses induced by elevation of extracellular K +, Both mechanisms are voltage sensitive and use extracellular Ca2+. T he fast but not the slow component was altered by changing the passive tension preload in a fashion consistent with a sliding filament mecha nism of force development. The specific nature of the slow component i s not certain but may involve low-level PKC activity and require the i ntegrity and capability for remodeling of a specific portion of the ac tin-containing cytoskeleton.