Unknown

Dataset Information

0

Bile acids potentiate proton-activated currents in Xenopus laevis oocytes expressing human acid-sensing ion channel (ASIC1a).


ABSTRACT: Acid-sensing ion channels (ASICs) are nonvoltage-gated sodium channels transiently activated by extracellular protons and belong to the epithelial sodium channel (ENaC)/Degenerin (DEG) family of ion channels. Bile acids have been shown to activate two members of this family, the bile acid-sensitive ion channel (BASIC) and ENaC. To investigate whether bile acids also modulate ASIC function, human ASIC1a was heterologously expressed in Xenopus laevis oocytes. Exposing oocytes to tauro-conjugated cholic (t-CA), deoxycholic (t-DCA), and chenodeoxycholic (t-CDCA) acid at pH 7.4 did not activate ASIC1a-mediated whole-cell currents. However, in ASIC1a expressing oocytes the whole-cell currents elicited by pH 5.5 were significantly increased in the presence of these bile acids. Single-channel recordings in outside-out patches confirmed that t-DCA enhanced the stimulatory effect of pH 5.5 on ASIC1a channel activity. Interestingly, t-DCA reduced single-channel current amplitude by ~15% which suggests an interaction of t-DCA with a region close to the channel pore. Molecular docking predicted binding of bile acids to the pore region near the degenerin site (G433) in the open conformation of the channel. Site-directed mutagenesis demonstrated that the amino acid residue G433 is critically involved in the potentiating effect of bile acids on ASIC1a activation by protons.

SUBMITTER: Ilyaskin AV 

PROVIDER: S-EPMC5309578 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications

Bile acids potentiate proton-activated currents in <i>Xenopus laevis</i> oocytes expressing human acid-sensing ion channel (ASIC1a).

Ilyaskin Alexandr V AV   Diakov Alexei A   Korbmacher Christoph C   Haerteis Silke S  

Physiological reports 20170201 3


Acid-sensing ion channels (ASICs) are nonvoltage-gated sodium channels transiently activated by extracellular protons and belong to the epithelial sodium channel (ENaC)/Degenerin (DEG) family of ion channels. Bile acids have been shown to activate two members of this family, the bile acid-sensitive ion channel (BASIC) and ENaC. To investigate whether bile acids also modulate ASIC function, human ASIC1a was heterologously expressed in <i>Xenopus laevis</i> oocytes. Exposing oocytes to tauro-conju  ...[more]

Similar Datasets

| S-EPMC5304176 | biostudies-other
| S-EPMC7351335 | biostudies-literature
| S-EPMC2839043 | biostudies-literature
| S-EPMC1219616 | biostudies-other
| S-EPMC4552029 | biostudies-literature
| S-EPMC6363413 | biostudies-literature
| S-EPMC5877580 | biostudies-literature
| S-EPMC5052465 | biostudies-literature
| S-EPMC7139892 | biostudies-literature
| S-EPMC6013169 | biostudies-literature