The pore region of the Kv1.2α subunit is an important component of recombinant Kv1.2 channel oxygen sensitivity
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文摘
Oxygen-sensitive K+ channels are important elements in the cellular response to hypoxia. Although much progress has been made in identifying their molecular composition, the structural components associated to their O2-sensitivity are not yet understood. Recombinant Kv1.2 currents expressed in Xenopus oocytes are inhibited by a decrease in O2 availability. On the contrary, heterologous Kv2.1 channels are O2-insensitive. To elucidate the protein segment responsible for the O2-sensitivity of Kv1.2 channels, we analyzed the response to anoxia of Kv1.2/Kv2.1 chimeric channels. Expression of chimeric Kv2.1 channels each containing the S4, the S1–S3 or the S6-COOH segments of Kv1.2 polypeptide resulted in a K+ current insensitive to anoxia. In contrast, transferring the S5–S6 segment of Kv1.2 into Kv2.1 produced an O2-sensitive K+ current. Finally, mutating a redox-sensitive methionine residue (M380) of Kv1.2 polypeptide did not affect O2-sensitivity. Thus, the pore and its surrounding regions of Kv1.2 polypeptide confer its hypoxic inhibition. This response is independent on the redox modulation of methionine residues in this protein segment.