Prevention by 7-oxo-prostacyclin of the calcium paradox in rat heart: role of the sarcolemmal (Na,K)-ATPase.
It is demonstrated a fast and significant depression in the sarcolemmal (Na,K)-ATPase activity that occurs as early as 25 sec after the onset of Ca2+ depletion, and participates in the development of Ca(2+)-paradox in the rat heart. Pretreatment of the animals with 7-oxo-prostacyclin (PGI2) 24-48 h prior to the experiment prevented fairly the Ca(2+)-depletion-induced depression in (Na,K)ATPase activity and the accompanying structural and functional damage to the heart and sarcolemma during Ca(2+)-depletion as well as the development of Ca(2+)-paradox during the subsequent Ca(2+)-repletion. Pretreatment with PGI2 was chosen intentionally because previous experiments revealed, that in its late effect the drug is acting via stabilizing the membranes due induction of high activity of (Na,K)-ATPase that has increased affinity to ATP. From results obtained the following may be concluded: If during the phase of Ca(2+)-deprivation, the capability of heart sarcolemma to maintain sodium extrusion remains preserved, the expected aggravation of Ca(2+)-overload injury to Ca(2+)-paradox that would develop during Ca(2+)-repletion, may be definitely prevented. Sufficiently preserved (Na,K)-ATPase activity, hand in hand with stabilized sarcolemmal structure, may prevent an accumulation of sodium beneath the sarcolemma and consequently also an overexcessive entry of Ca2+ into the myocytes.
Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovak Republic.
A
A
Ziegelhöffer
T
T
Ravingerová
A
A
Dzurba
N
N
Tribulová
J
J
Slezák
A
A
Breier
L
L
Szekeres
D000818:Animals; D002118:Calcium / Q000502:physiology*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D012508:Sarcolemma / Q000201:enzymology*; D012964:Sodium / Q000378:metabolism; D019831:Sodium-Calcium Exchanger; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D002352:Carrier Proteins; D019831:Sodium-Calcium Exchanger; C033705:7-oxoprostaglandin I2; D012964:Sodium; D011464:Epoprostenol; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium