| Autor: |
Sun HL; Riley Heart Research Center, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.; Department of Pharmacology, Harbin Medical University-Daqing, Daqing, Heilongjiang, China., Tsai WC; The Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.; Division of Cardiology, Department of Medicine, Hualein Tzu-Chi General Hospital, Hualein, Taiwan., Li BY; Department of Biomedical Engineering, Indiana University-Purdue University at Indianapolis, Indianapolis, Indiana, United States of America., Tao W; Riley Heart Research Center, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, United States of America., Chen PS; The Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States of America., Rubart M; Riley Heart Research Center, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, United States of America. |
| Abstrakt: |
Recent studies have provided evidence that depolarization in the absence of extracellular Ca2+ can trigger Ca2+ release from internal stores in a variety of neuron subtypes. Here we examine whether postganglionic sympathetic neurons are able to mobilize Ca2+ from intracellular stores in response to depolarization, independent of Ca2+ influx. We measured changes in cytosolic ΔF/F0 in individual fluo-4 -loaded sympathetic ganglion neurons in response to maintained K+ depolarization in the presence (2 mM) and absence of extracellular Ca2+ ([Ca2+]e). Progressive elevations in extracellular [K+]e caused increasing membrane depolarizations that were of similar magnitude in 0 and 2 mM [Ca2+]e. Peak amplitude of ΔF/F0 transients in 2 mM [Ca2+]e increased in a linear fashion as the membrane become more depolarized. Peak elevations of ΔF/F0 in 0 mM [Ca2+]e were ~5-10% of those evoked at the same membrane potential in 2 mM [Ca2+]e and exhibited an inverse U-shaped dependence on voltage. Both the rise and decay of ΔF/F0 transients in 0 mM [Ca2+]e were slower than those of ΔF/F0 transients evoked in 2 mM [Ca2+]e. Rises in ΔF/F0 evoked by high [K+]e in the absence of extracellular Ca2+ were blocked by thapsigargin, an inhibitor of endoplasmic reticulum Ca2+ ATPase, or the inositol 1,4,5-triphosphate (IP3) receptor antagonists 2-aminoethoxydiphenyl borate and xestospongin C, but not by extracellular Cd2+, the dihydropyridine antagonist nifedipine, or by ryanodine at concentrations that caused depletion of ryanodine-sensitive Ca2+ stores. These results support the notion that postganglionic sympathetic neurons possess the ability to release Ca2+ from IP3-sensitive internal stores in response to membrane depolarization, independent of Ca2+ influx. |
