Angiotensin regulates the selectivity of the Na+-K+ pump for intracellular Na+.
Treatment of rabbits with angiotensin-converting enzyme (ACE) inhibitors increases the apparent affinity of the Na+-K+ pump for Na+. To explore the mechanism, we voltage clamped myocytes from control rabbits and rabbits treated with captopril with patch pipettes containing 10 mM Na+. When pipette solutions were K+ free, pump current (Ip) for myocytes from captopril-treated rabbits was nearly identical to that for myocytes from controls. However, treatment caused a significant increase in Ip measured with pipettes containing K+. A similar difference was observed when myocytes from rabbits treated with the ANG II receptor antagonist losartan and myocytes from controls were compared. Treatment-induced differences in Ip were eliminated by in vitro exposure to ANG II or phorbol 12-myristate 13-acetate or inclusion of the protein kinase C fragment composed of amino acids 530-558 in pipette solutions. Treatment with captopril had no effect on the voltage dependence of Ip. We conclude that ANG II regulates the pump's selectivity for intracellular Na+ at sites near the cytoplasmic surface. Protein kinase C is implicated in the messenger cascade.
Buhagiar
K A
KA
Department of Cardiology, Royal North Shore Hospital, St. Leonards 2065, Australia.
Hansen
P S
PS
Gray
D F
DF
Mihailidou
A S
AS
Rasmussen
H H
HH
D000804:Angiotensin II / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000809:Angiotensins / Q000502:physiology*; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D004594:Electrophysiology; D004789:Enzyme Activation / Q000502:physiology; D005110:Extracellular Space / Q000378:metabolism; D006352:Heart Ventricles; D007425:Intracellular Membranes / Q000378:metabolism*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D011817:Rabbits; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism* / Q000502:physiology
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000809:Angiotensins; D000804:Angiotensin II; D002216:Captopril; D012964:Sodium; D011493:Protein Kinase C; D000254:Sodium-Potassium-Exchanging ATPase; D019808:Losartan; D011188:Potassium