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• W2007536003 abstract "Recently, we have shown that Rho and Rho-activated kinase (ROCK) may become activated by high-millimolar KCl, which had previously been widely assumed to act solely through opening of voltage-dependent Ca 2+ channels. In this study, we explored in more detail the relationship between membrane depolarization, Ca 2+ currents, and activation of Rho/ROCK in bovine tracheal smooth muscle. Ca 2+ currents began to activate at membrane voltages more positive than −40 mV and were maximally activated above 0 mV; at the same time, these underwent time- and voltage-dependent inactivation. Depolarizing intact tissues by KCl challenge evoked contractions that were blocked equally, and in a nonadditive fashion, by nifedipine or by the ROCK inhibitor Y-27632. Other agents that elevate intracellular calcium concentration ([Ca 2+ ] i ) by pathways independent of G protein-coupled receptors, namely the SERCA-pump inhibitor cyclopiazonic acid and the Ca 2+ ionophore A-23187, evoked contractions that were also largely reduced by Y-27632. KCl directly increased Rho and ROCK activities in a concentration-dependent fashion that paralleled closely the effect of KCl on tone and [Ca 2+ ] i , as well as the voltage-dependent Ca 2+ currents that were measured over the voltage ranges that are evoked by 0–120 mM KCl. Through the use of various pharmacological inhibitors, we ruled out roles for Ca 2+ /calmodulin-dependent CaM kinase II, protein kinase C, and protein kinase A in mediating the KCl-stimulated changes in tone and Rho/ROCK activities. In conclusion, Rho is activated by elevation of [Ca 2+ ] i (although the signal transduction pathway underlying this Ca 2+ dependence is still unclear) and possibly also by membrane depolarization per se." @default.
• W2007536003 created "2016-06-24" @default.
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• W2007536003 date "2005-10-01" @default.
• W2007536003 modified "2023-10-16" @default.
• W2007536003 title "Regulation of Rho/ROCK signaling in airway smooth muscle by membrane potential and [Ca²⁺]_i" @default.
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• W2007536003 doi "https://doi.org/10.1152/ajplung.00134.2005" @default.
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