Characterization of an angiotensin-II-activated chloride current in rabbit sino-atrial cells.
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.
Bescond
J
J
Laboratoire de Physiologie Générale, CNRS U.R.A. 1869, Faculté des Sciences, Université de Poitiers, France.
Bois
P
P
Petit-Jacques
J
J
Lenfant
J
J
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism*; D004159:Diphenylamine / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D008564:Membrane Potentials; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011817:Rabbits; D012849:Sinoatrial Node / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D000873:Anthracenes; D018118:Chloride Channels; D002712:Chlorides; D000804:Angiotensin II; C059537:3',5-dichlorodiphenylamine-2-carboxylic acid; C010030:9-anthroic acid; D004159:Diphenylamine; D011493:Protein Kinase C