Inhibition of SERCA pumps induces desynchronized RyR activation in overloaded internal Ca2+ stores in smooth muscle cells

Gomez-Viquez NL, Guerrero-Serna G, Arvizu F, Garcia U, Guerrero-Hernandez A. Inhibition of SERCA pumps induces desynchronized RyR activation in overloaded internal Ca2+ stores in smooth muscle cells. Am J Physiol Cell Physiol 298: C1038-C1046, 2010. First published January 27, 2010; doi:10.1152/ajpcell.00222.2009.-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 (Gomez-Viquez L, Guerrero-Serna G, Garcia U, Guerrero-Hernandez 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.