K+-Induced Smooth Muscle Calcium Sensitization Requires RhoA Kinase (ROK) Translocation to Caveolae Which Is Inhibited in Non-Neuronal Cell Memory

<p>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.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biological Sciences

Year dc:date.available

2003

Author dc:creator

• Urban, Nicole Hairrell

Contributors dc:contributor

• Paul H. Ratz
• Howard W. White
• Russell Prewitt
• Mark Elliott
• Jeff Dupree

• Calcium sensitization
• Caveolae
• Cell memory
• Potassium
• RhoA kinase
• Smooth muscle
• Biochemistry
• Biophysics

Identifier

9780496549467

OAI identifier oai:identifier

oai:digitalcommons.odu.edu:biomedicalsciences_etds-1138