Characterization of the heteromeric potassium channel formed by kv2.1 and the retinal subunit kv8.2 in Xenopus oocytes.
Kv8.2 (KCNV2) subunits do not form homotetrameric potassium channels, although they coassemble with Kv2.1 to constitute functional heteromers. High expression of Kv8.2 was reported in the human retina and its mutations were linked to the visual disorder "cone dystrophy with supernormal rod electroretinogram." We detected abundant Kv8.2 expression in the photoreceptor layer of mouse retina, where Kv2.1 is also known to be present. When the two subunits were coexpressed in Xenopus oocytes in equal amounts, Kv8.2 abolished the current of Kv2.1. If the proportion of Kv8.2 was reduced then the current of heteromeric channels emerged. Kv8.2 shifted the steady-state activation of Kv2.1 to more negative potentials, without affecting the voltage dependence of inactivation. This gave rise to a window current within the -40 to -10 mV membrane potential range. Ba2+ inhibited the heteromeric channel and shifted its activation to more positive potentials. These electrophysiological and pharmacological properties resemble those of the voltage-gated K+ current (named I Kx) described in amphibian retinal rods. Furthermore, oocytes expressing Kv2.1/Kv8.2 developed transient hyperpolarizing overshoots in current-clamp experiments, whereas those expressing only Kv2.1 failed to do so. Similar overshoots are characteristic responses of photoreceptors to light flashes. We demonstrated that Kv8.2 G476D, analogous to a disease-causing human mutation, eliminated Kv2.1 current, if the subunits were coexpressed equally. However, Kv8.2 G476D did not form functional heteromers under any conditions. Therefore we suggest that the custom-tailored current of Kv2.1/Kv8.2 functionally contributes to photoreception, and this is the reason that mutations of Kv8.2 lead to a genetic visual disorder.
Czirják
Gábor
G
Department of Physiology, Semmelweis University of Medicine, P.O. Box 259, Budapest, Hungary H-1444.
Tóth
Zsuzsanna E
ZE
Enyedi
Péter
P
D000818:Animals; D003001:Cloning, Molecular; D005260:Female; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics / Q000502:physiology*; D021122:Protein Subunits; D012313:RNA / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D012160:Retina / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051669:Shab Potassium Channels / Q000235:genetics / Q000502:physiology*; D014981:Xenopus
C496991:Kcnb1 protein, rat; D024642:Potassium Channels, Voltage-Gated; D021122:Protein Subunits; D012333:RNA, Messenger; D051669:Shab Potassium Channels; D012313:RNA