Korean J Physiol Pharmacol Vol 16: 219－224, June, 2012 http://dx.doi.org/10.4196/kjpp.2012.16.3.219 Gap Junction Contributions to the Goldfish Electroretinogram at the Photopic Illumination Level Doh-Yeon Kim, and Chang-Sub Jung Natural Sciences Section, Department of Medical Lifescience, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea Understanding how the b-wave of the electroretinogram (ERG) is generated by full-field light stimulation is still a challenge in visual neuroscience. To understand more about the origin of the b-wave, we studied the contributions of gap junctions to the ERG b-wave. Many types of retinal neurons are connected to similar and different neighboring neurons through gap junctions. The photopic (cone-dominated) ERG, stimulated by a small light beam, was recorded from goldfish (Carassius auratus) using a corneal electrode. Data were obtained before and after intravitreal injection of agents into the eye under a photopic illumination level. Several agents were used to affect gap junctions, such as dopamine D1 and D2 receptor agonists and antagonists, a nitric oxide (NO) donor, a nitric oxide synthase (NOS) inhibitor, the gap junction blocker meclofenamic acid (MFA), and mixtures of these agents. The ERG b-waves, which were enhanced by MFA, sodium nitroprusside (SNP), SKF 38393, and sulpiride, remained following application of a further injection of a mixture with MFA. The ERG b-waves decreased following NG-nitro-L-arginine methyl ester (L-NAME), SCH 23390, and quinpirole administration but were enhanced by further injection of a mixture with MFA. These results indicate that gap junction activity influences b-waves of the ERG related to NO and dopamine actions. Key Words: Electroretinogram, b-wave, Gap-junction, Nitric oxide, Dopamine INTRODUCTION Bipolar cells, located in the outer nuclear layer and called second order neurons, have synapses with photoreceptors, horizontal cells, and interplexiform cells (IPCs). It is known that bipolar cells are contrast detectors [1] that relay sig- nals from the photoreceptors to ganglion cells, because bipo- lar cells initially have a center-surround antagonistic re- ceptive field [2,3]. Many results suggest that the surround receptive fields of bipolar cells are provided by horizontal cells with large receptive fields [4,5]. Coupling of gap junc- tion channels located in the horizontal cell membrane pro- vides the large receptive fields of the horizontal cells. Most retinal cells have over 70 types of electrical gap junctions between similar or different neurons within the vertebrate retina, including gap junctions between bipolar cells [6-9]. As the receptive fields of bipolar cells are provided by the outer retinal cells [3-5], it is arguing how the light activities Received May 3, 2012, Revised May 29, 2012, Accepted May 30, 2012 Corresponding to: Chang-Sub Jung, Natural Sciences Section, Department of Medical Lifescience, College of Medicine, The Catholic University of Korea, #222, Banpo-daero, Seocho-gu, Seoul 137-701, Korea. (Tel) 82-2-2588-7241, (Fax) 82-2-2258-7761, (E-mail) cjung@ catholic.ac.kr This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http:// creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 219 of bipolar cells will really happen in vivo when gap junction conductance in the outer retinal neurons are changed. Gap junction modulators include nitric oxide (NO) and dopamine (DA), which act through the intracellular mes- sengers cGMP and cAMP, respectively [10-16]. Application of sodium nitroprusside (SNP, a NO donor) or 8-bromo- cGMP to pairs of cultured horizontal cells decreases the am- plitude of the gap junction coupling current. The uncoup- ling of horizontal cell soma by DA is accompanied by a de- crease in gap junction particle density and is caused by re- ducing both the duration and frequency of channel opening [17,18]. The results of these actions are to offer the possi- bility that bipolar cell light activity can be modulated by both NO and/or DA relating to gap-junction coupling. To study the effects of gap junction coupling on bipolar cell light activities, we recorded corneal electroretinogram (ERG) b-waves under a photopic illumination level before and after intravitreal injection of meclofenamic acid (MFA), a well-known non-specific gap junction blocker, NO, and DA-related (DA, SKF 38393, quinpirole, SCH 23390, sulpir- ide) drugs, and also co-applied these drugs with MFA. Here, we show that MFA strongly amplified corneal ERG b-waves compared to that of the control. After increasing b-wave amplitude with NO and dopamine, no further increase was observed by co-applying these drugs and MFA. Our results ABBREVIATIONS: ERG, electroretinogram; NO, nitric oxide; NOS, nitric oxide synthase; MFA, meclofenamic acid; SNP, sodium nitro- prusside; L-NAME, NG-nitro-L-arginine methyl ester; IPC, inter- plexiform cell; DA, dopamine; NADPH-d, nicotinamide dinucleotide phosphate diaphorase.