Characteristics for Enhanced Response of Serotonin-Evoked Ion Dynamics in Differentiated NG108-15 Cells

Characteristics for the up-regulated response in the concentration of intracellular calcium ion ([Ca 2+ ] i ) and in the sodium ion (Na + ) current by serotonin (5-HT) were investigated in differentiated neuroblastoma × glioma hybrid NG108-15 (NG) cells. The results for the changes in [Ca 2+ ] i by 5-HT were as follows, (1) The 5-HT-induced Ca 2+ response was inhibited by 3 × 10 −9 M tropisetron (a 5-HT 3 receptor blocker), but not by other types of 5-HT receptor blockers; (2) The 5-HT-induced Ca 2+ response was mainly inhibited by calciseptine (a L-type Ca 2+ blocker), but not by other types of Ca 2+ channel blockers or 10 −7 M TTX (a voltage-sensitive Na + channel blocker); (3) When the extracellular Na + was removed by exchange with choline chloride or N -methyl- d -glucamine, the 5-HT-induced Ca 2+ response was extremely inhibited. The results for the 5-HT-induced Na + current by the whole cell patch-clamp technique were as follows, (1) The 5-HT-induced Na + current in differentiated cells was significantly larger than that in undifferentiated cells; (2) The ED 50 value for 5-HT-induced Na + current in undifferentiated and differentiated cells was almost the same, about 4 × 10 −6 M each other; (3) The 5-HT-induced Na + current was completely blocked by 3 × 10 −9 M tropisetron, but not by other 5-HT receptor antagonists and 10 −7 M TTX. These results suggested that 5-HT-induced Ca 2+ response in differentiated NG cells was mainly due to L-type voltage-gated Ca 2+ channels allowing extracellular Na + to enter via 5-HT 3 receptors, but not through voltage-gated Na + channels.