Changes in activation gating of IsK potassium currents brought about by mutations in the transmembrane sequence

FEBS Letters

Sivaprasadarao, Asipu²  Wilson, Gary G.²  Wray, Dennis²  Findlay, John B.C.¹ 

[1] Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, UK;Departments of Pharmacology, University of Leeds, Leeds LS2 9JT, UK

关键词: Potassium channel;    Delayed rectifier;   

DOI  :  10.1016/0014-5793(94)01058-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown