Relevance of the proximal domain in the amino‐terminus of HERG channels for regulation by a phospholipase C‐coupled hormone receptor

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Abstract
We used Xenopus oocytes co-expressing thyrotropin-releasing hormone (TRH) receptors and human ether-a-go-go-related gene (HERG) K+ channel variants carrying different amino-terminal modifications to check the relevance of the proximal domain for hormonal regulation of the channel. Deletion of the whole proximal domain (Δ138–373) eliminates TRH-induced modifications in activation and deactivation parameters. TRH effects on activation are also suppressed with channels lacking the second half of the proximal domain or only residues 326–373. However, normal responses to TRH are obtained with Δ346–373 channels. Thus, whereas residues 326–345 are required for the hormonal modulation of HERG activation, different proximal domain sequences contribute to set HERG gating characteristics and its regulation by TRH