Biophysical properties of amiloride-sensitive sodium channels (ASSC) in human B lymphocytes

Academic Article

Abstract

  • The biophysical characteristics of single ASSCs in EBV-transformed B lymphocytes from unaffected individuals and those with Liddle's Disease (due to activating mutations of the subunit of the channel) were studies with the cell-attached configuration of the patch clamp technique. Typically, the patches were relatively quiescent in unstimulated control (Daudi) cells, and the frequency of the inward single channel events increased substantially after superfusion with 40 μM 8-CPT-cAMP. The biophysical characteristics of the inward single channel currents are shown the table, including number of channel events (n), open and closed probability, unit conductance (cond. pS), and the time constants for channel opening and closing (τO and τC) Cell Type (n) %open %closed Cond. (pS) to(ma) tc(ma) Daudi Basal 988 6% 94% 6.3 3.8 11-5 Daudi cAMP 717 13% 87% 6.3 5.3 10.3 Liddle's Basal 735 12% 88% 6.5 3.2 11.0 Liddle's cAMP 491 17% 83% 6.7 5.1 8.6 Additional analysis was performed to determine if the single channels which were activated by cAMP were responsible for the amiloride-sensitive inward whole-cell current that is activated in human B lymphocytes by cAMP. This analysis showed that summed ensemble single channel recordings corrected for reasonable estimates of the number of channels per lymphocyte reproduced the average magnitude and kinetic behavior of the cAMP-activated amiloride-sensitive whole-cell currents. These findings provide strong evidence for the hypothesis that the single channels described herein are responsible for the activated ASSCs that are characteristic of Liddle's Disease.
  • Published In

    Author List

  • Bubien JK; Warnock DG
  • Volume

  • 44
  • Issue

  • 3