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Changes in activation gating of I sK potassium currents brought about by mutations in the transmembrane sequence
Author(s) -
Wilson Gary G.,
Sivaprasadarao Asipu,
Findlay John B.C.,
Wray Dennis
Publication year - 1994
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(94)01058-7
Subject(s) - transmembrane domain , xenopus , gating , mutant , potassium channel , mutagenesis , amino acid , biophysics , transmembrane protein , chemistry , protein subunit , site directed mutagenesis , cysteine , kcsa potassium channel , ion channel , biology , biochemistry , gene , receptor , enzyme
Expression of the rat kidney I sK protein in Xenopus oocytes produces slowly‐activating potassium channel currents. We have investigated the relationship between structure and function of the single putative membrane‐spanning domain using site‐directed mutagenesis. Six mutants were constructed in which consecutive individual amino acids (53 to 58) of the transmembrane region were substituted by cysteine. Expression of four of these mutants in Xenopus oocytes resulted in currents which were similar to wild‐type. However, for one mutant (position 55) activation curves were shifted in a hyperpolarising direction and for another mutant (position 58) activation curve were shifted in a depolarising direction. This suggests that the hydrophobic phenylalanine residues at positions 55 and 58 may play a critical role in I sK activation gating. This spacing of functional amino acids at every third residue may indicate an α‐helical conformation for the membrane‐spanning domain of I sK . Furthermore, these results also indicate that one face of the helix may represent a region of subunit association.