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.
","abstract_html":"<p>KC1 causes smooth muscle contraction by elevating intracellular free calcium ([Ca<sup>2+</sup>]i<sub>)</sub>, while receptor stimulation activates an additional mechanism termed Ca<sup>2+</sup>- sensitization that can involve activation of ROK and PKC. However, recent studies support the hypothesis that KC1 may also increase Ca<sup>2+</sup>-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 Ca<sup>2+</sup>-activated Ca<sup>2+</sup>-sensitization, elicited by KC1 contraction, that involves Ca<sup>2</sup>+/cam dependent ROK translocation to caveolae and activation by RhoA.</p>","abstract_has_math":false,"creators":["Urban, Nicole Hairrell"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation","degree_discipline":"Biological Sciences","degree_department":null,"school":null,"contributors":["Paul H. Ratz","Howard W. White","Russell Prewitt","Mark Elliott","Jeff Dupree"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2003,"date_issued":"2003-07-01T07:00:00Z","date_published":"2003-07-01T07:00:00Z","updated_at":"2026-07-24T03:35:23Z","subjects":["Calcium sensitization","Caveolae","Cell memory","Potassium","RhoA kinase","Smooth muscle","Biochemistry","Biophysics"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["9780496549467"],"render_values":[{"text":"9780496549467","href":null,"code":true}]}]},"links":{"outbound_url":"https://digitalcommons.odu.edu/biomedicalsciences_etds/136","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Paul H. Ratz","Howard W. White","Russell Prewitt","Mark Elliott","Jeff Dupree"]},{"key":"dc:creator","label":"Author","values":["Urban, Nicole Hairrell"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2019-10-17T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biological Sciences"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Calcium sensitization","Caveolae","Cell memory","Potassium","RhoA kinase","Smooth muscle","Biochemistry","Biophysics"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["9780496549467","https://digitalcommons.odu.edu/biomedicalsciences_etds/136"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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.
"]},{"key":"dc:title","label":"Title","values":["K+-Induced Smooth Muscle Calcium Sensitization Requires RhoA Kinase (ROK) Translocation to Caveolae Which Is Inhibited in Non-Neuronal Cell Memory"]}]}],"canonical_facts":{"dc:contributor":["Paul H. Ratz","Howard W. White","Russell Prewitt","Mark Elliott","Jeff Dupree"],"dc:creator":["Urban, Nicole Hairrell"],"dc:date.available":["2019-10-17T07:00:00Z"],"dc:description.abstract":["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.
"],"dc:identifier":["9780496549467","https://digitalcommons.odu.edu/biomedicalsciences_etds/136"],"dc:subject":["Calcium sensitization","Caveolae","Cell memory","Potassium","RhoA kinase","Smooth muscle","Biochemistry","Biophysics"],"dc:title":["K+-Induced Smooth Muscle Calcium Sensitization Requires RhoA Kinase (ROK) Translocation to Caveolae Which Is Inhibited in Non-Neuronal Cell Memory"],"thesis:degree_discipline":["Biological Sciences"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T03:35:23Z"}