Genetic inactivation of an inwardly rectifying potassium channel (Kir4.1 subunit) in mice: phenotypic impact in retina.
The inwardly rectifying potassium channel Kir4.1 has been suggested to underlie the principal K(+) conductance of mammalian Müller cells and to participate in the generation of field potentials and regulation of extracellular K(+) in the retina. To further assess the role of Kir4.1 in the retina, we generated a mouse line with targeted disruption of the Kir4.1 gene (Kir4.1 -/-). Müller cells from Kir4.1 -/- mice were not labeled with an anti-Kir4.1 antibody, although they appeared morphologically normal when stained with an anti-glutamine synthetase antibody. In contrast, in Müller cells from wild-type littermate (Kir4.1 +/+) mice, Kir4.1 was present and localized to the proximal endfeet and perivascular processes. In situ whole-cell patch-clamp recordings showed a 10-fold increase in the input resistance and a large depolarization of Kir4.1 -/- Müller cells compared with Kir4.1 +/+ cells. The slow PIII response of the light-evoked electroretinogram (ERG), which is generated by K(+) fluxes through Müller cells, was totally absent in retinas from Kir4.1 -/- mice. The b-wave of the ERG, in contrast, was spared in the null mice. Overall, these results indicate that Kir4.1 is the principal K(+) channel subunit expressed in mouse Müller glial cells. The highly regulated localization and the functional properties of Kir4.1 in Müller cells suggest the involvement of this channel in the regulation of extracellular K(+) in the mouse retina.
Kofuji
P
P
Departments of Neuroscience and Physiology, University of Minnesota, Minneapolis 55455, USA. kofuj001@t.umn.edu
Ceelen
P
P
Zahs
K R
KR
Surbeck
L W
LW
Lester
H A
HA
Newman
E A
EA
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D001253:Astrocytes / Q000737:chemistry / Q000502:physiology; D017097:Electric Impedance; D004596:Electroretinography; D015870:Gene Expression / Q000502:physiology; D015640:Ion Channel Gating / Q000235:genetics; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D018408:Patch-Clamp Techniques; D010641:Phenotype; D015221:Potassium Channels / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D012160:Retina / Q000737:chemistry* / Q000166:cytology / Q000502:physiology*
D000906:Antibodies; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger