strychnine and nickel-chloride

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

Topics: Animals; Bicuculline; Calcium Channels; Calcium Channels, R-Type; Cation Transport Proteins; Cattle; Dose-Response Relationship, Drug; Drug Combinations; Electroretinography; GABA Antagonists; gamma-Aminobutyric Acid; Glycine Agents; In Vitro Techniques; Nickel; Night Vision; Phosphinic Acids; Photoreceptor Cells, Vertebrate; Pyridines; Receptors, Glycine; Retina; Signal Transduction; Strychnine