In the retinas of Royal College of Surgeons (RCS) rats light induces an increase in distal extracellular potassium irrespective of the age, between days 19-24 and days 29-35 postpartum, but by days 29-35 the ERG b-wave has become reduced. The synaptic blocker 2-amino-4-phosphonobutyric acid (APB) causes the abolition of both the b-wave and the potassium increase at any age. MgCl2 greatly reduces the b-wave at all ages and abolishes the potassium increase in older rats, but in younger rats the potassium increase is enlarged. Since this increase occurs in the absence of the b-wave it is unlikely that the on-bipolar cells are the only sources of the b-wave. Because the NMDA receptor blocker ketamine reduces the b-wave, third order neurons, which possess NMDA receptors, could contribute to the b-wave.

The ERG and the extracellular potassium concentration, [K+]o, of the isolated superfused rat retina were measured in a physiological solution and in solutions containing 10 mM MgCl2 or 100 mu M APB. MgCl2 nearly abolished the b-wave, but the light-induced distal [K+]o increase was enlarged from 0.13 +/- 0.05 to 0.28 +/- 0.08 mM. There was also an increase in the light-induced [K+]o in the proximal retina. APB abolished the b-wave completely, and the distal light-induced [K+]o increase was then replaced by a [K+]o decrease. Upon return to the control solution, there was a larger transitory [K+]o increase than under control conditions, and this occurred before the b-wave had returned. Under these experimental conditions, the distal [K+]o increase could not be correlated with the b-wave, and so the Muller cells are unlikely to be the main source of the rising phase of the b-wave. More probable sources of the b-wave are the on-bipolar cells with their metabotropic and ionotropic receptors, with only the latter apparently being blocked by MgCl2. The extracellular [K+]o changes, however, had an influence upon the slow potentials of the ERG.

The retina of the Royal College of Surgeons (RCS) strain of rat, which is being used as an animal model for human retinal degenerations, has been employed in the study of the function of second order neurons. By about the 33rd postnatal day the dendritic branching of isolated bipolar cells is more sparse than in bipolar cells of the normal rat retina, but their GABA channels are as in the normal rat retina. The normally occurring light-induced distal potassium increase has been used as the indicator of the functional competence of second order neurons in the isolated RCS rat retina. These are dependent upon the integrity of ionotropic and metabotropic synapses. At about the 22nd postnatal day MgCl₂ enlarges the light-induced distal potassium increase in the young RCS rat retina as in the normal rat retina. It seems that MgCl₂ does not block the metabotropic synapses of on-bipolar cells. At about postnatal day 33, at which time the photoreceptors of the RCS rat retina had become severely damaged, the size of this light-induced distal potassium increase was not changed, but it was abolished by MgCl₂. This indicates that bipolar cells are still active but that the synaptic function of on-bipolar cells has become vulnerable to MgCl₂. The conclusion is that at a time when photoreceptor degeneration is already severe bipolar cells are still active, but that on-bipolars, mainly rod bipolar cells, have some functional deficit.

Although the rising phase of the b-wave seems to be generated mainly in the rod bipolar cells and the cone on-bipolar cells, the slow component of the electroretinogram, the c-wave, evidently originates in the Müller cells and the pigment epithelium. The c-wave has three components. One cornea-positive component derives from the pigment epithelium, while a distal cornea-negative component (slow PIII) and a proximal slow component originate in the Müller cells. This third proximal component of the c-wave differs between mammalian species: it is negative in the rat retina, positive in the rabbit and human retina and may be lacking in the cat retina.

When preparing isolated rabbit retinas we found in some animals fundi which were not uniformly dark but had abnormal areas of red coloration. The in situ electroretinograms (ERG) of 82 rabbits recorded after 1 h of dark adaptation were checked for abnormalities indicative of a degenerative disorder. The ERGs of eight rabbits with small dark adapted b-waves (< or = 250 microV) were re-recorded and their b-waves found to decline with time. The greatest reduction, in three rabbits, was > or = 150 microV over 2.5 years. After 1 year, however, the light adapted b-waves were similar to those of rabbits with normal dark adapted b-waves. The majority of the progeny of these rabbits also had small b-waves, which became still smaller in 2 years. Ultrastructural studies of two rabbit retinas of the first generation showed pathological changes of the pigment epithelium (Wrigstad, Hanitzsch & Nilsson, Ultrastructural and electrophysiological studies of the retina and the retinal pigment epithelium in rabbits with low b-wave amplitudes, in preparation). Evidently there is an inheritable defect in the pigment epithelium which first impairs the rod pathway.