Origin of the Nose Component in Mouse ERG

Abstract

Purpose: : The leading edge of the a-wave of the ERG is generally believed to reflect the photocurrent of photoreceptors. The aspartate-isolated mammalian ERG response to rod-saturating flash contains a peak component (nose) timely overlapping with the a-wave (Arden (1976), J. Physiol. 256, 333-361). The purpose of this study was to elucidate the mechanism generating the nose.

Methods: : Photoresponses to flashes (2 - 20 ms) were recorded with the ERG technique across isolated mouse (Mus musculus) retinas or across retinal layers with microelectrodes (T = 25 ^oC). The b-wave and higher-order neuron components were blocked with 2 mM aspartate. The glial component (slow PIII) was removed by barium.

Results: : The nose component was not present in the outer segment layer but became apparent in the inner segment layer of the retina. A significant portion (up to 80-90 %) of the saturated rod ERG signal was derived in the inner segment layer. Pure cone responses did not contain any significant nose component while the cone-free rod responses included the nose. Lowering the free [Ca²⁺]_out from 1 mM to ~25 nM removed the nose. The Ca²⁺-channel blockers Cd²⁺ and Co²⁺ or the intracellular Ca²⁺ buffer BAPTA(-AM) did not affect the nose component. The h-channel blockers Cs⁺ (2 - 5 mM) and ZD7288 (50 µM) removed the nose. Both blockers increased the saturated photoresponse amplitude when measured at plateau level following the nose. Potassium channel blockers TEA (20 mM) and Ba²⁺ (10 mM) decreased the nose amplitude.

Conclusions: : The nose in the mouse ERG is generated in the inner segments of rod photoreceptors. We propose a following model for the nose mechanism: In darkness a "sodium loop" circulates between the Na⁺/K⁺ pumps located in the distal part of the inner segment and the cGMP channels in the outer segment, while a "potassium loop" circulates between the Na⁺/K⁺ pumps and potassium channels located more proximally along the inner segment. During the saturated response "the sodium loop" current goes to zero while the potassium loop current follows the "peak-plateau" process of membrane potential (Fain et al. (1978), Nature, 272, 466-9) generated by the hyperpolarization-activated h-channels. If the h-channels are located proximal to the Na⁺/K⁺ pumps, the h current can produce an additional contribution to the nose.

Keywords: electroretinography: non-clinical • photoreceptors • ion channels