Norma Leticia Gómez-Viquez
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Guadalupe Guerrero-Serna
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Fernando Arvizu
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Ubaldo García
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Agustín Guerrero-Hernández
We have previously shown that rapid inhibition of sarcoplasmic reticulum (SR) ATPase (SERCA pumps) decreases the amplitude and rate of rise (synchronization) of caffeine induced-Ca2+ release without producing a reduction of free luminal SR Ca2+ level in smooth muscle cells (Gómez-Viquez L, Guerrero-Serna G, García U, Guerrero-Hernández A. Biophys J 85: 370–380, 2003). Our aim was to investigate the role of luminal SR Ca2+ content in the communication between ryanodine receptors (RyRs) and SERCA pumps. To this end, we studied the effect of SERCA pump inhibition on RyR-mediated Ca2+ release in smooth muscle cells with overloaded SR Ca2+ stores. Under this condition, the amplitude of RyR-mediated Ca2+ release was not affected but the rate of rise was still decreased. In addition, the caffeine-induced Ca2+-dependent K+ outward currents revealed individual events, suggesting that SERCA pump inhibition reduces the coordinated activation of RyRs. Collectively, our results indicate that SERCA pumps facilitate the activation of RyRs by a mechanism that does not involve the regulation of SR Ca2+ content. Importantly, SERCA pumps and RyRs colocalize in smooth muscle cells, suggesting a possible local communication between these two proteins.