Institute of Neurophysiology, University of Cologne, Germany.
Acta Ophthalmol. 2009 Nov;87(8):854-65. doi: 10.1111/j.1755-3768.2008.01387.x.
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.
NiCl₂（15 μM）通过阻断 E/R 型电压门控 Ca²⁺通道，将脊椎动物视网膜的视网膜电图（ERG）b 波幅度刺激高达 1.5 倍。假设这种增加是通过离子型 GABA 受体阻断抑制性神经递质 γ-氨基丁酸（GABA）的释放来介导的，我们测试了 GABA 本身和 GABA 受体拮抗剂（如（-）bicuculline（增加 1.5 倍）和（1,2,5,6-四氢吡啶-4-基）甲基膦酸（TPMPA；增加 1.46 倍）对 b 波幅度的影响。
从分离的牛视网膜记录视网膜电流。
当首先施加 15 μM NiCl₂时，GABA（100 μM）仅降低 b 波幅度。每种拮抗剂单独应用仅部分刺激 b 波幅度：随后施加 NiCl₂超滤液导致小但额外的增加，导致 Ni²⁺加（-）bicuculline或 Ni²⁺加 TPMPA的幅度分别增加 1.69 倍和 1.88 倍。只有在低 NiCl₂（15 μM）之前同时应用两种拮抗剂，才能完全防止 NiCl₂随后的刺激，并导致 b 波幅度总增加 1.90 倍。那些对 NiCl₂没有反应的视网膜段不能被（-）bicuculline刺激，反之亦然。
NiCl₂对 ERG b 波幅度的刺激作用主要但不是唯一通过 NiCl₂敏感的 Ca（v）2.3 触发的 GABA 释放来介导，该释放通过离子型 GABA-A 和 GABA-C 受体起作用。
