Voltage-Induced Ca2+ Release in Postganglionic Sympathetic Neurons in Adult Mice

Recent studies have provided evidence that depolarization in the absence of extracellular Ca 2+ can trigger Ca 2+ release from internal stores in a variety of neuron subtypes. Here we examine whether postganglionic sympathetic neurons are able to mobilize Ca 2+ from intracellular stores in response to depolarization, independent of Ca 2+ influx. We measured changes in cytosolic ΔF/F 0 in individual fluo-4 –loaded sympathetic ganglion neurons in response to maintained K + depolarization in the presence (2 mM) and absence of extracellular Ca 2+ ([Ca 2+ ] e ). Progressive elevations in extracellular [K + ] e caused increasing membrane depolarizations that were of similar magnitude in 0 and 2 mM [Ca 2+ ] e . Peak amplitude of ΔF/F 0 transients in 2 mM [Ca 2+ ] e increased in a linear fashion as the membrane become more depolarized. Peak elevations of ΔF/F 0 in 0 mM [Ca 2+ ] e were ~5–10% of those evoked at the same membrane potential in 2 mM [Ca 2+ ] e and exhibited an inverse U-shaped dependence on voltage. Both the rise and decay of ΔF/F 0 transients in 0 mM [Ca 2+ ] e were slower than those of ΔF/F 0 transients evoked in 2 mM [Ca 2+ ] e . Rises in ΔF/F 0 evoked by high [K + ] e in the absence of extracellular Ca 2+ were blocked by thapsigargin, an inhibitor of endoplasmic reticulum Ca 2+ ATPase, or the inositol 1,4,5-triphosphate (IP 3 ) receptor antagonists 2-aminoethoxydiphenyl borate and xestospongin C, but not by extracellular Cd 2+ , the dihydropyridine antagonist nifedipine, or by ryanodine at concentrations that caused depletion of ryanodine-sensitive Ca 2+ stores. These results support the notion that postganglionic sympathetic neurons possess the ability to release Ca 2+ from IP 3 -sensitive internal stores in response to membrane depolarization, independent of Ca 2+ influx.