Voltage-Induced Ca(2+) 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.