Regulation of Na+ channels by luminal Na+ in rat cortical collecting tubule

J Physiol. 1998 May 15;509 ( Pt 1)(Pt 1):151-62. doi: 10.1111/j.1469-7793.1998.151bo.x.

Abstract

1. The idea that luminal Na+ can regulate epithelial Na+ channels was tested in the cortical collecting tubule of the rat using whole-cell and single-channel recordings. Here we report results consistent with the idea of Na+ self-inhibition. 2. Macroscopic amiloride-sensitive currents (INa) were measured by conventional whole-cell clamp. INa was a saturable function of external Na+ concentration ([Na+]o) with an apparent Km of 9 mM. Single channel currents (iNa) were measured in cell-attached patches. iNa increased with pipette Na+ concentration with an apparent Km of 48 mM. Since INa = (iNa)NPo, the different Km values imply that the channel density (N) and/or open probability (Po) increase as [Na+]o decreases. Reduction of [Na+]o after increasing intracellular Na+ concentration also increased the outward amiloride-sensitive conductance, consistent with activation of the Na+ channels. 3. The underlying mechanism was studied by changing pipette Na+ concentration while recording from cell-attached patches. No increase in NPo was observed, suggesting that the effect is not a direct interaction between [Na+]o and the channel. 4. [Na+]o was varied outside the patch-clamp pipette while recording from cell-attached patches. When amiloride was in the bath to prevent Na+ entry, no change in NPo was observed. 5. Activation of the channels by hyperpolarization was observed with 140 mM Na+o but not with 14 mM Na+o. 6. The results are consistent with the concept of self-inhibition of Na+ channels by luminal Na+. Activation of the channels by lowering [Na+]o is not additive with that achieved by hyperpolarization.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenine Nucleotides / pharmacology
  • Animals
  • Down-Regulation / drug effects
  • Down-Regulation / physiology
  • Electric Stimulation
  • Electrophysiology
  • Female
  • Guanine Nucleotides / pharmacology
  • Kidney Cortex / drug effects
  • Kidney Cortex / physiology*
  • Kidney Tubules, Collecting / drug effects
  • Kidney Tubules, Collecting / physiology*
  • Kinetics
  • Male
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Patch-Clamp Techniques
  • Rats
  • Rats, Sprague-Dawley
  • Sodium / physiology*
  • Sodium Channels / drug effects
  • Sodium Channels / physiology*

Substances

  • Adenine Nucleotides
  • Guanine Nucleotides
  • Sodium Channels
  • Sodium