Regulation of TRPV5 single-channel activity by intracellular pH

Seung Kuy Cha, Wasey Jabbar, Jian Xie, Chou Long Huang

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

The transient receptor potential channel TRPV5 contributes to the apical entry pathway for transcellular calcium reabsorption in the kidney. Acid load causes hypercalciuria in animals and humans. We have previously reported that intracellular protons directly inhibit TRPV5. Here, we examined the effects of intracellular pH on single-channel activity of TRPV5. We found that TRPV5 channels exhibit full and subconductance open states in excised inside-out patches of Chinese hamster ovary cells. The slope conductance values (Na + as a charge carrier, between -25 and -75 mV) for full and subconductance opening at intracellular pH 7.4 were 59 ± 6 and 29 ± 3 pS, respectively. Intracellular acidification caused a small decrease in single-channel conductance. Importantly, intracellular acidification decreased open probability for the full and subconductance states and increased probability for closing. To investigate how intracellular protons decrease open probability of the channel, we proposed a simple three-state model for open-subconductance-closed state transition and examined the effects of acidification on the respective forward and reverse rate constants. We found that intracellular acidification decreases opening of TRPV5 predominantly by promoting a transition from the subconductance to the closed state. Thus, intracellular acidification directly inhibits TRPV5 by causing a conformational change(s) leading to a decrease of open probability of TRPV5 as well as of the single-channel conductance.

Original languageEnglish (US)
Pages (from-to)79-85
Number of pages7
JournalJournal of Membrane Biology
Volume220
Issue number1-3
DOIs
StatePublished - Dec 1 2007

Keywords

  • Chinese hamster ovary cell
  • Intracellular pH
  • Open probability
  • Subconductance state
  • TRPV5

ASJC Scopus subject areas

  • Biophysics
  • Physiology
  • Cell Biology

Fingerprint Dive into the research topics of 'Regulation of TRPV5 single-channel activity by intracellular pH'. Together they form a unique fingerprint.

  • Cite this