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. 2004 Sep 1:10:650-4.

Contribution of Kir4.1 to the mouse electroretinogram

Jiang Wu  1 , Alan D Marmorstein, Paulo Kofuji, Neal S Peachey
Affiliations

Contribution of Kir4.1 to the mouse electroretinogram

Jiang Wu et al. Mol Vis. .

Abstract

Purpose: The electroretinogram (ERG) represents the combination of several distinct cellular processes and conductances. Here, we define the contribution that K+ conductance through Kir4.1 channels makes to the mouse ERG.

Methods: To obtain mice expressing different levels of Kir4.1, we mated Kir4.1+/- mice and used PCR to identify Kir4.1+/- and Kir4.1+/+ littermates. In addition, we mated Kir4.1+/- males with females homozygous for the nob (no b-wave) defect, which eliminates post-receptoral contributions to the ERG. After overnight dark adaptation, mice were anesthetized and ERGs were recorded to 7 min stimuli, to focus on slow ERG components, or to strobe flash stimuli, to examine earlier ERG components.

Results: The amplitudes of the ERG c-wave and the fast oscillation, measured from the c-wave peak, were significantly larger in Kir4.1+/- mice than in Kir4.1+/+ littermates. In comparison, the amplitude of the light peak, the other main component generated by the retinal pigment epithelium in response to light, did not differ between Kir4.1+/- and Kir4.1+/+ mice. The amplitude of slow PIII, revealed by the nob genetic background, was reduced in Kir4.1+/- mice.

Conclusions: These results indicate that a cornea-negative potential, generated by Kir4.1, normally opposes a positive polarity conductance that is generated by the apical membrane of the retinal pigment epithelium to form the c-wave measured at the corneal surface.

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Figures

Figure 1
Figure 1
Comparison of ERGs obtained to 7 min stimuli from control and Kir4.1 mutant mice. ERGs recorded to 7 min duration stimulus flashes from Kir4.1+/+ (thin blue tracings) or Kir4.1+/− (thick red tracings) mice. Each record indicates the grand average of 3 Kir4.1+/+ or 8 Kir4.1+/− mice. The stimulus intensity used to evoke these responses is indicated on the left. Stimulus presentation is represented by the lower trace. Amplitude calibration indicates 1 mV.
Figure 2
Figure 2
Intensity response functions for the amplitude of the major ERG components generated by the RPE in response to light. The different panels plot the amplitude of the c-wave (A), fast oscillation (B), light peak (C), or off response (D) as a function of flash intensity (black line, C57BL/6J; red line, Kir4.1+/−; blue line, Kir4.1+/+). Data points indicate the average of 3 to 8 responses obtained from different mice; the error bars represent the standard error of the mean. Note that Kir4.1+/+ mice were tested using only a subset of the stimulus intensities.
Figure 3
Figure 3
Comparison of strobe flash ERGs obtained from control and Kir4.1 mutant mice. ERGs recorded to strobe flash stimuli from Kir4.1+/+/nob (thin blue tracing) or Kir4.1+/−/nob (thick red tracing) mice. Each record indicates the grand average of 5 Kir4.1+/+/nob or 7 Kir4.1+/−/nob mice. Stimulus intensity was −0.03 log cd sec/m2
Figure 4
Figure 4
Comparison of ERGs obtained to 7 min stimuli from control and Kir4.1 mutant mice. ERGs recorded to 7 min duration stimulus flashes from Kir4.1+/+/nob (thin blue tracing) or Kir4.1+/−/nob (thick red tracing) mice. Each record indicates the grand average of 3 Kir4.1+/+/nob or 7 Kir4.1+/−/nob mice. Stimulus intensity was 2.2 cd/m2. Stimulus presentation is represented by the lower trace. Amplitude calibration indicates 1 mV.
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