Open AccessThe asparagine 533 residue in the outer pore loop region of the mouse PKD 2L1 channel is essential for its voltage‐dependent inactivation
Author(s) -
Shimizu Takahiro,
Higuchi Taiga,
Toba Toshihiro,
Ohno Chie,
Fujii Takuto,
Nilius Bernd,
Sakai Hideki
Publication year - 2017
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.12273
Subject(s) - depolarization , biophysics , chemistry , asparagine , membrane potential , bacterial outer membrane , extracellular , mutant , microbiology and biotechnology , biology , biochemistry , amino acid , escherichia coli , gene
Voltage‐dependent inactivation of ion channels contributes to the regulation of the membrane potential of excitable cells. Mouse polycystic kidney disease 2‐like 1 ( PKD 2L1) forms voltage‐dependent nonselective cation channels, which are activated but subsequently inactivated in response to membrane depolarization. Here, we found that the mutation of an asparagine 533 residue (N533Q) in the outer pore loop region of PKD 2L1 caused a marked increase in outward currents induced by depolarization. In addition, the tail current analysis demonstrated that the N533Q mutants are activated during depolarization but the subsequent inactivation does not occur. Interestingly, the N533Q mutants lacked the channel activation triggered by the removal of stimuli such as extracellular alkalization and heating. Our findings suggest that the N533 residue in the outer pore loop region of PKD 2L1 has a key role in the voltage‐dependent channel inactivation.