Antagonists of ionotropic gamma-aminobutyric acid receptors impair the NiCl2-mediated stimulation of the electroretinogram b-wave amplitude from the isolated superfused vertebrate retina.
OBJECTIVE
NiCl(2) (15 microM) stimulates the electroretinogram (ERG) b-wave amplitude of vertebrate retina up to 1.5-fold through its blocking of E/R-type voltage-gated Ca(2+) channels. Assuming that such an increase is mediated by blocking the release of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) via ionotropic GABA receptors, we tested the effect of both GABA itself and GABA-receptor antagonists such as (-)bicuculline (1.51-fold increase) and (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA; 1.46-fold increase) on the b-wave amplitude.


METHODS
Recording of the transretinal potentials from the isolated bovine retina.


RESULTS
GABA (100 microM) reduced the b-wave amplitude only when NiCl(2) (15 microM) was applied first. Each antagonist applied on its own stimulated the b-wave amplitude only partially: subsequent NiCl(2) superfusion caused a small but additional increase, leading to a 1.69- and a 1.88-fold total increase of the amplitude by Ni(2+) plus (-)bicuculline or Ni(2+) plus TPMPA, respectively. Only the application of both antagonists in combination, before superfusing low NiCl(2) (15 microM), completely prevented subsequent stimulation by NiCl(2) with a similar 1.90-fold total increase of b-wave amplitude. Those retina segments that did not respond to NiCl(2) could not be stimulated by (-)bicuculline and vice versa.


CONCLUSIONS
The stimulatory effect of NiCl(2) on the ERG b-wave amplitude is mainly, but not only, mediated by a NiCl(2)-sensitive, Ca(v)2.3-triggered GABA release acting through ionotropic GABA-A and GABA-C receptors.
Siapich
Siarhei A
SA
Institute of Neurophysiology, University of Cologne, Germany.
Banat
Mohammed
M
Albanna
Walid
W
Hescheler
Jürgen
J
Lüke
Matthias
M
Schneider
Toni
T
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology*; D015220:Calcium Channels; D020908:Calcium Channels, R-Type; D027682:Cation Transport Proteins; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004596:Electroretinography / Q000187:drug effects*; D018756:GABA Antagonists / Q000494:pharmacology*; D018684:Glycine Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D009532:Nickel / Q000494:pharmacology*; D055254:Night Vision; D010721:Phosphinic Acids / Q000494:pharmacology*; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology*; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D013331:Strychnine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage
C101879:(1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid; C423009:CACNA1E protein, human; D015220:Calcium Channels; D020908:Calcium Channels, R-Type; D027682:Cation Transport Proteins; D004338:Drug Combinations; D018756:GABA Antagonists; D018684:Glycine Agents; D010721:Phosphinic Acids; D011725:Pyridines; D018009:Receptors, Glycine; D005680:gamma-Aminobutyric Acid; C022838:nickel chloride; D009532:Nickel; D013331:Strychnine; D001640:Bicuculline