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Related Experiment Videos

Phosphate stimulates CFTR Cl- channels

M R Carson1, S M Travis, M C Winter

  • 1Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.

Biophysical Journal
|November 1, 1994
PubMed
Summary
This summary is machine-generated.

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Inorganic phosphate (P(i)) stimulates Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) chloride channel activity by increasing its open probability. This suggests P(i) may play a regulatory role in CFTR function.

Area of Science:

  • Molecular biology
  • Ion channel physiology
  • Biochemistry

Background:

  • Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) chloride channels are crucial for ion transport.
  • CFTR activity is regulated by ATP hydrolysis, with ADP inhibiting function.
  • The role of inorganic phosphate (P(i)), another hydrolysis product, in CFTR regulation was unclear.

Purpose of the Study:

  • To investigate the effect of inorganic phosphate (P(i)) on CFTR chloride channel activity.
  • To elucidate the mechanism by which P(i) influences CFTR channel gating.

Main Methods:

  • Excised inside-out patch-clamp technique to record single-channel CFTR activity.
  • Dose-response analysis of P(i) on channel activity.
  • Kinetic modeling to determine the effect of P(i) on channel gating parameters.

Related Experiment Videos

  • Binding studies using photoactivatable ATP analogs.

    • Main Results:

    • Millimolar concentrations of P(i) caused a dose-dependent stimulation of CFTR channel activity.
    • P(i) increased single-channel open-state probability (po), not conductance.
    • Kinetic modeling indicated P(i) increased the rate of transition from closed to bursting states.
    • P(i) potentiated ATP-stimulated activity and stimulated CFTR mutants lacking the R domain.
    • Binding studies showed P(i) decreased bound nucleotide levels.

    Conclusions:

    • Inorganic phosphate (P(i)) stimulates CFTR chloride channel activity.
    • P(i) likely acts by increasing the rate-limiting step in channel opening, potentially via interaction with nucleotide-binding domains.
    • These findings reveal a novel regulatory mechanism for CFTR function.