O2-sensitive K+ channels: role of the Kv1.2 alpha-subunit in mediating the hypoxic response

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O₂-sensitive K⁺ channels: role of the Kv1.2 $alpha$ -subunit in mediating the hypoxic response

Laura Conforti *, Ilona Bodi ¹, John W. Nisbet and David E. Millhorn

Department of Molecular and Cellular Physiology, * Department of Internal Medicine, Division of Nephrology and Hypertension and ¹Institute of Molecular Pharmacology and Biophysics, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA

One of the early events in O₂ chemoreception is inhibition of O₂-sensitive K⁺ (K_O₂) channels. Characterization of the molecular composition of the native K_O₂ channels in chemosensitive cells is important to understand the mechanism(s) that couple O₂ to the K_O₂ channels.
The rat phaeochromocytoma PC12 clonal cell line expresses an O₂-sensitive voltage-dependent K⁺ channel similar to that recorded in other chemosensitive cells. Here we examine the possibility that the Kv1.2 $alpha$ -subunit comprises the K_O₂ channel in PC12 cells.
Whole-cell voltage-clamp experiments showed that the K_O₂ current in PC12 cells is inhibited by charybdotoxin, a blocker of Kv1.2 channels.
PC12 cells express the Kv1.2 $alpha$ -subunit of K⁺ channels: Western blot analysis with affinity-purified anti-Kv1.2 antibody revealed a band at ~80 kDa. Specificity of this antibody was established in Western blot and immunohystochemical studies. Anti-Kv1.2 antibody selectively blocked Kv1.2 current expressed in the Xenopus oocyte, but had no effect on Kv2.1 current.
Anti-Kv1.2 antibody dialysed through the patch pipette completely blocked the K_O₂ current, while the anti-Kv2.1 and irrelevant antibodies had no effect.
The O₂ sensitivity of recombinant Kv1.2 and Kv2.1 channels was studied in Xenopus oocytes. Hypoxia inhibited the Kv1.2 current only.
These findings show that the K_O₂ channel in PC12 cells belongs to the Kv1 subfamily of K⁺ channels and that the Kv1.2 $alpha$ -subunit is important in conferring O₂ sensitivity to this channel.

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