Alloxan-induced diabetes reduces sarcolemmal Na+-K+ pump function in rabbit ventricular myocytes.
The effect of diabetes on sarcolemmal Na(+)-K(+) pump function is important for our understanding of heart disease associated with diabetes and design of its treatment. We induced diabetes characterized by hyperglycemia but no other major metabolic disturbances in rabbits. Ventricular myocytes isolated from diabetic rabbits and controls were voltage clamped and internally perfused with the whole cell patch-clamp technique. Electrogenic Na(+)-K(+) pump current (I(p), arising from the 3:2 Na(+)-to-K(+) exchange ratio) was identified as the shift in holding current induced by Na(+)-K(+) pump blockade with 100 micromol/l ouabain in most experiments. There was no effect of diabetes on I(p) recorded when myocytes were perfused with pipette solutions containing 80 mmol/l Na(+) to nearly saturate intracellular Na(+)-K(+) pump sites. However, diabetes was associated with a significant decrease in I(p) measured when pipette solutions contained 10 mmol/l Na(+). The decrease was independent of membrane voltage but dependent on the intracellular concentration of K(+). There was no effect of diabetes on the sensitivity of I(p) to extracellular K(+). Pump inhibition was abolished by restoration of euglycemia or by in vivo angiotensin II receptor blockade with losartan. We conclude that diabetes induces sarcolemmal Na(+)-K(+) pump inhibition that can be reversed with pharmacological intervention.
Hansen
Peter S
PS
Dept. of Cardiology, Royal North Shore Hospital, St. Leonards, NSW 2065, Australia.
Clarke
Ronald J
RJ
Buhagiar
Kerrie A
KA
Hamilton
Elisha
E
Garcia
Alvaro
A
White
Caroline
C
Rasmussen
Helge H
HH
D000496:Alloxan; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage; D000818:Animals; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D006352:Heart Ventricles / Q000473:pathology / Q000503:physiopathology*; D015640:Ion Channel Gating / Q000187:drug effects*; D019808:Losartan / Q000008:administration & dosage*; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000378:metabolism*
D047228:Angiotensin II Type 1 Receptor Blockers; D000496:Alloxan; D000254:Sodium-Potassium-Exchanging ATPase; D019808:Losartan