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 sarcolemma l (Na,K)-ATPase activity that occurs as early as 25 sec after the onse t of Ca2+ depletion, and participates in the development of Ca2+-parad ox in the rat heart. Pretreatment of the animals with 7-oxo-prostacycl in (PGI2) 24-48 h prior to the experiment prevented fairly the Ca2+-de pletion-induced depression in (Na,K)ATPase activity and the accompanyi ng structural and functional damage to the heart and sarcolemma during Ca2+-depletion as well as the development of Ca2+-paradox during the subsequent Ca2+-repletion. Pretreatment with PGI(2) was chosen intenti onally 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 re sults obtained the following may be concluded: If during the phase of Ca2+-deprivation, the capability of heart sarcolemma to maintain sodiu m extrusion remains preserved, the expected aggravation of Ca2+-overlo ad injury to Ca2+-paradox that would develop during Ca2+-repletion, ma y be definitely prevented. Sufficiently preserved (Na,K)-ATPase activi ty, hand in hand with stabilized sarcolemmal structure, may prevent an accumulation of sodium beneath the sarcolemma and consequently also a n overexcessive entry of Ca2+ into the myocytes.