Early activation of Ca(2+)-permeable AMPA receptors reduces neurite outgrowth in embryonic chick retinal neurons.
Calcium entry through Ca(2+)-permeable AMPA/kainate receptors may activate signaling cascades controlling neuronal development. Using the fluorescent Ca(2+)-indicator Calcium Green 1-AM we showed that the application of kainate or AMPA produced an increase of intracellular [Ca(2+)] in embryonic chick retina from day 6 (E6) onwards. This Ca(2+) increase is due to entry through AMPA-preferring receptors, because it was blocked by the AMPA receptor antagonist GYKI 52466 but not by the N-methyl-D-aspartic acid (NMDA) receptor antagonist AP5, the voltage-gated Ca(2+) channel blockers diltiazem or nifedipine, or by the substitution of Na+ for choline in the extracellular solution to prevent the depolarizing action of kainate and AMPA. In dissociated E8 retinal cultures, application of glutamate, kainate, or AMPA reduced the number of neurites arising from these cells. The effect of kainate was prevented by the AMPA/kainate receptor antagonist CNQX and by GYKI 52466 but not by AP5, indicating that the reduction in neurite outgrowth resulted from the activation of AMPA receptors. Blocking Ca(2+) influx through L-type voltage-gated Ca(2+) channels with diltiazem and nifedipine prevented the effect of 10-100 microM kainate but not that of 500 microM kainate. In addition, joro spider toxin-3, a blocker of Ca(2+)-conducting AMPA receptors, prevented the effect of all doses of kainate. Neither GABA, which is depolarizing at this age in the retina, nor the activation of metabotropic glutamate receptors with tACPD mimicked the effects of AMPA receptor activation. Calcium entry via AMPA receptor channels themselves may therefore be important in the regulation of neurite outgrowth in developing chick retinal cells.
Catsicas
M
M
Department of Physiology, University College London, Gower Street, London WC1E 6BT, United Kingdom.
Allcorn
S
S
Mobbs
P
P
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001569:Benzodiazepines; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D020013:Calcium Signaling; D002642:Chick Embryo; D046508:Culture Techniques; D003952:Diagnostic Imaging; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D016501:Neurites / Q000502:physiology* / Q000648:ultrastructure; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D018091:Receptors, AMPA / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D012160:Retina / Q000166:cytology* / Q000196:embryology / Q000378:metabolism
D014151:Anti-Anxiety Agents; D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; C061950:GYKI 52466; D001569:Benzodiazepines; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D002118:Calcium