The early receptor potential (ERP) was first discovered by Brown and Murakami,³ who were recording a local electroretinogram (ERG) with an electrode placed within the photoreceptor layer of the monkey retina and were stimulating with a very bright light. What they saw (figure 40.1) was a rapid response having no detectable latency, which they called the early receptor potential, or early RP, followed by the a-wave of the ERG. The polarity of the ERP was the same as that of the a-wave of the ERG, which in their experiments was positive-going. They then showed that the ERP was remarkably resistant to anoxia, suggesting that it was produced not by activation of the transduction cascade, but rather by some other movement of charge within the photoreceptor.

Figure 40.1.  

Discovery of ERP. The traces give same recording at two different sweep speeds. The records show potential recorded from the retina of a cynomolgus monkey (Macaca irus) with a tungsten microelectrode inserted into the layer of the photoreceptors. The reference electrode was placed in the vitreous. Notice that with this configuration, the a-wave is positive-going, opposite in polarity to the a-wave of the ERG recorded conventionally with a corneal electrode (see figure 40.2). Photoreceptors were stimulated with bright light from a condenser-discharge lamp. Stimulus artifact appears as break in record in upper trace. (Modified and reprinted with permission from Brown and Murakami.³)

Richard Cone⁴ subsequently demonstrated that the ERP could be detected with the same configuration of electrodes and amplifier used to measure the ERG. The polarity of the major component of the ERP was again the same as that of the a-wave, but when the active electrode was placed at the cornea or in the vitreous, both the ERP and the a-wave were negative-going (figure 40.2). Cone also demonstrated that in the rat, the spectral sensitivity of the ERP matched that of the rod pigment and that the amplitude of the major component of the ERP increased nearly linearly with the intensity of the stimulus and saturated at about the light level required to bleach all of the pigment in the photoreceptor. These observations showed that the ERP is produced directly by the photopigment, probably by the movement of charge within the rhodopsin molecule that is triggered by the changes in conformation produced by bleaching.

Figure 40.2.  

ERP recorded from a 38-year-old man with ocular siderosis. The recording was made with monopolar corneal contact lens. The patient had sustained traumatic injury to his right eye by penetration of a metal fragment containing a high iron concentration. Even though the a- and b-waves of the involved eye were substantially reduced (not shown), the amplitude of the ERP in the right eye was approximately the same as that in the left (uninjured) eye. (Modified and reprinted with permission from Sieving et al.¹⁸)

Once it became feasible to make intracellular recordings routinely from vertebrate photoreceptors, it was possible to show that the electrical events that are responsible for the ERP can be produced in both rods¹⁵ and cones¹¹ and that they have properties in single receptors identical to those originally inferred from measurements of whole retina. In most recordings, the ERP can be seen to have two components, usually called R1 and R2 (figure 40.3). The R1 component is an initial depolarization with a latency less than 0.5µs⁵ or perhaps even smaller.¹⁹ The R2 component is hyperpolarizing, develops with a longer latency, and is usually considerably larger in amplitude. It is this R2 component that is responsible for the signal that Brown and Murakami originally recorded (see figure 40.1).

Figure 40.3.  

Intracellular recording of ERP from turtle cone stimulated with xenon flash. The upper trace shows the waveform of the flash. Note the two components of the ERP labeled R1 and R2. (Modified and reprinted with permission from Hodgkin and O’Bryan.¹¹)

Since the ERP can be detected intracellularly from single photoreceptors as a change in membrane potential (as in figure 40.3) or as a membrane current from cells that have been voltage clamped,^10,12,13 we may conclude that it is caused by the movement of charge with some component perpendicular to the plane of the plasma membrane. Because the size of the ERP is proportional to the number of pigment molecules bleached by the stimulus, it is apparently produced by changes in the conformation of the rhodopsin molecule that move either charged amino acids or associated bound charges (such as H⁺) across the plasma membrane. A simple calculation shows that the amplitude of the R2 component can be accounted for by the movement of a single charge a distance of a few angstroms.^7,10,11,13 The amplitude of the ERP would be expected to be larger in cones than in rods, since all of the photopigment in a cone is embedded in the plasma membrane, whereas for rods, only a small fraction of the rhodopsin lies in the plasma membrane or in the few basal disks that are continuous with the plasma membrane. This would explain why, in humans, the rods make a smaller contribution to the ERP of the whole retina (see, e.g., Goldstein and Berson⁹ and Sieving and Fishman¹⁷), even though rods are nearly 20 times more numerous than cones.

Because the R1 and R2 components have different time courses and are of opposite polarity, they are likely to be produced by different conformational changes of the rhodopsin molecule. They are easily separated from one another by reducing temperature, which blocks R2 (see, e.g., Pak and Ebrey¹⁶), and they have been extensively studied.⁷ The R1 component is probably produced by some change that occurs between the absorption of a photon and the formation of the pigment intermediate metarhodopsin I.^5,6,16 The R2 component, on the other hand, probably reflects the movement of charge during the transition from metarhodopsin I to the active intermediate metarhodopsin II or R*. These charge movements are reversible.^2,5 That is, one flash of light can be used to convert rhodopsin to metaI, producing R1, and another can then be given to photoreverse the metaI back to rhodopsin, producing a charge movement that is identical in waveform to R1 but opposite in sign.