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 x 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 x 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 x 10(-6) M each other; (3) The 5-HT-induced Na(+) current was completely blocked by 3 x 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.
Imanishi
Takashi
T
Department of Pharmacy, Laboratory of Biological Chemistry, School of Pharmacy, Kinki University, Higashiosaka, Japan.
Matsushima
Kayoko
K
Kawaguchi
Akinori
A
Asano
Hajime
H
Funakami
Yoshinori
Y
Wada
Tetsuyuki
T
Masuko
Takashi
T
Yoshida
Shigeru
S
Ichida
Seiji
S
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology; D002413:Cations, Divalent; D002414:Cations, Monovalent; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D006822:Hybrid Cells; D015640:Ion Channel Gating; D051379:Mice; D018408:Patch-Clamp Techniques; D051381:Rats; D044406:Receptors, Serotonin, 5-HT3 / Q000502:physiology; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D012964:Sodium / Q000502:physiology*; D015222:Sodium Channels / Q000502:physiology
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D002413:Cations, Divalent; D002414:Cations, Monovalent; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D015222:Sodium Channels; D012701:Serotonin; D012964:Sodium; D002118:Calcium