Characterization of an angiotensin-II-activated chloride current in rabbit sino-atrial cells

J Membr Biol. 1994 Jun;140(2):153-61. doi: 10.1007/BF00232903.

Abstract

Single sino-atrial cells from rabbit heart were voltage-clamped using the whole-cell configuration of the patch clamp technique under conditions in which most of the ionic and exchange currents known in pacemaker cardiac cells were minimized. Extracellular angiotensin II (AII) activated a time-independent background current. The current-voltage relation of this current showed an outward rectification. The reversal potential was -20 mV with 156 mM Cl- external solution and 54 mM Cl- internal solution. This reversal potential shifted with changes in the transmembrane Cl- gradient in the fashion expected for a chloride current. Anthracene-9-carboxylic acid and diphenylamine-2-carboxylic acid (chloride channels blockers) were found to be effective in blocking the AII-sensitive current. The linear segment of the current-voltage relation can be totally inhibited by the competitive AII-receptor (AT1) antagonist losartan and by the presence of intracellular protein kinase C inhibitor, whereas the outward rectification is only slightly changed. It is concluded that sino-atrial cells should contain protein-kinase-C-sensitive chloride channels which may be activated by angiotensin II via the stimulation of the AT1 receptors.

MeSH terms

  • Angiotensin II / antagonists & inhibitors
  • Angiotensin II / pharmacology*
  • Animals
  • Anthracenes / pharmacology
  • Chloride Channels / antagonists & inhibitors
  • Chloride Channels / drug effects
  • Chloride Channels / metabolism
  • Chlorides / metabolism*
  • Diphenylamine / analogs & derivatives
  • Diphenylamine / pharmacology
  • In Vitro Techniques
  • Membrane Potentials
  • Patch-Clamp Techniques
  • Protein Kinase C / antagonists & inhibitors
  • Rabbits
  • Sinoatrial Node / cytology
  • Sinoatrial Node / drug effects
  • Sinoatrial Node / metabolism*

Substances

  • Anthracenes
  • Chloride Channels
  • Chlorides
  • Angiotensin II
  • 3',5-dichlorodiphenylamine-2-carboxylic acid
  • 9-anthroic acid
  • Diphenylamine
  • Protein Kinase C