Contribution of Kir4.1 to the mouse electroretinogram

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.