Abstract
In SH-SY5Y cells we have shown that stimulation with high extracellular K + ([K +] e) evokes a transient increase in cytoplasmic Ca 2+ ([Ca 2+] cyt) (K + on) that is triggered by the opening of voltage-dependent Ca 2+ channels and followed by Ca 2+-induced Ca 2+ release from the endoplasmic reticulum (Xu, F., Zhang, J., Recio-Pinto, E. and Blanck, T.J., Halothane and isoflurane augment depolarization-induced cytosolic CA2+ transients and attenuate carbachol-stimulated CA2+ transients, Anesthesiology, 92 (2000) 1746–56). The removal of high-[K +] e results in a second transient increase in [Ca 2+] cyt (K + off) that is independent of extracellular Ca 2+ (Corrales, A., Montoya, G.J., Sutachan, J.J., Cornillez-Ty, G., Garavito-Aguilar, Z., Xu, F., Blanck, T.J. and Recio-Pinto, E., Transient increases in extracellular K+ produce two pharmacological distinct cytosolic Ca2+ transients, Brain Res., 1031 (2005) 174–184). In this study we further characterize the properties of K + off. We found that K + off was detectable at near physiological temperatures (34–36 °C) but, depending on the level of [K +] e, it was undetectable or highly diminished at room temperature. In contrast, K + on was increased by lowering the temperature. Extracellular Na +-replacement with K + did not affect K + off, indicating that K + off was not generated by osmolarity changes. Replacement of extracellular Na + with choline + did not affect K + off, indicating that K + off did not result from activity changes of the plasma membrane Na +/Ca 2+ exchanger. Caffeine decreased K + on but not K + off. CCCP (carbonyl cyanide m-chlorophenyl), a protonophore uncoupler that decreases mitochondrial Ca 2+ uptake, decreased K + on but not K + off. CGP37157, an inhibitor of the mitochondria Na +/Ca 2+ exchanger, decreased K + off when added alone but not when added simultaneously with CCCP. Clonazepam had similar effects as CGP37157. These findings indicate that the generation of K + off is strongly temperature-dependent and its pharmacology is distinct from the [Ca 2+] cyt changes observed previously at room temperature.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have