Characterization of an early-diverging KCNE potassium-channel auxiliary subunit in the jawless vertebrate lamprey

The KCNE (KCNE1–6) proteins are single-pass transmembrane auxiliary subunits of the voltage-gated K ⁺ channel KCNQ1. KCNQ1–KCNE complexes have been well studied in jawed vertebrates ranging from zebrafish to humans, but KCNE subunits from earlier-diverging vertebrates remain poorly characterized. Here, we functionally characterize a single KCNE-like gene in lamprey, a jawless vertebrate, and designate it kcne0 as an early-diverging member of the KCNE family. KCNE0 shows moderate amino acid sequence similarity to KCNE1–6 but is not particularly similar to any single isoform. Both kcnq1 and kcne0 transcripts were detected in multiple lamprey organs. When co-expressed with lamprey KCNQ1, KCNE0 produced a constitutively active current, similar to KCNE3. By contrast, KCNE0 modulated KCNQ1 from other species less effectively, suggesting species-specific tuning of KCNQ1–KCNE compatibility. Introducing into KCNE0 an intracellular tetra-leucine motif analogous to that in KCNE4 markedly reduced KCNQ1 current amplitude, conferring a KCNE4-like inhibitory effect. Overall, this work provides a functional reference for comparing KCNE-dependent modulation of KCNQ1 across vertebrates and suggests an underlying compatibility mechanism.