Connexins regulate calcium signaling by controlling ATP release.
Forced expression of gap junction proteins, connexins, enables gap junction-deficient cell lines to propagate intercellular calcium waves. Here, we show that ATP secretion from the poorly coupled cell lines, C6 glioma, HeLa, and U373 glioblastoma, is potentiated 5- to 15-fold by connexin expression. ATP release required purinergic receptor-activated intracellular Ca2+ mobilization and was inhibited by Cl- channel blockers. Calcium wave propagation also was reduced by purinergic receptor antagonists and by Cl- channel blockers but insensitive to gap junction inhibitors. These observations suggest that cell-to-cell signaling associated with connexin expression results from enhanced ATP release and not, as previously believed, from an increase in intercellular coupling.
Cotrina
M L
ML
Departments of Cell Biology and Anatomy, New York Medical College, Valhalla, NY 10595, USA.
Lin
J H
JH
Alves-Rodrigues
A
A
Liu
S
S
Li
J
J
Azmi-Ghadimi
H
H
Kang
J
J
Naus
C C
CC
Nedergaard
M
M
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000502:physiology*; D018031:Connexin 43 / Q000502:physiology; D017630:Connexins / Q000502:physiology*; D005909:Glioblastoma; D005910:Glioma; D006367:HeLa Cells; D006801:Humans; D008856:Microscopy, Fluorescence; D051381:Rats; D015398:Signal Transduction; D019284:Thapsigargin / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured; D000097002:Gap Junction beta-1 Protein
D000251:Adenosine Triphosphatases; D002118:Calcium; D018031:Connexin 43; D017630:Connexins; D019284:Thapsigargin; D000097002:Gap Junction beta-1 Protein