Date of Award
Doctor of Philosophy (PhD)
Paul H. Ratz
Howard W. White
KC1 causes smooth muscle contraction by elevating intracellular free calcium ([Ca2+]i), while receptor stimulation activates an additional mechanism termed Ca2+- sensitization that can involve activation of ROK and PKC. However, recent studies support the hypothesis that KC1 may also increase Ca2+-sensitivity (36). Our data showed that the PKC inhibitor, GF-109203X, did not, while the ROK inhibitor, Y-27632, did inhibit KCl-induced tonic (5’) force and myosin light chain (MLC) phosphorylation in rabbit artery. Y-27632 also inhibited Bay K-8644- and ionomycin-induced MLC phosphorylation and force, but did not inhibit KCl-induced calcium entry or peak (~15”) force. Moreover, KC1 and Bay K-8644 nearly doubled the amount o f ROK colocalized to caveolae at 30”, a time that preceded inhibition of force by Y-27632. Colocalization was not inhibited by Y-27632, but was abolished by nifedipine and the calmodulin blocker, trifluoperazine. Since, -30% of RhoA is colocalized with caveolin basally, these data suggest a novel model for Ca2+-activated Ca2+-sensitization, elicited by KC1 contraction, that involves Ca2+/cam dependent ROK translocation to caveolae and activation by RhoA.
Urban, Nicole H..
"K+-Induced Smooth Muscle Calcium Sensitization Requires RhoA Kinase (ROK) Translocation to Caveolae Which Is Inhibited in Non-Neuronal Cell Memory"
(2003). Doctor of Philosophy (PhD), dissertation, Biological Sciences, Old Dominion University, DOI: 10.25777/7qhc-0737