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 Ca²⁺-paradox in the rat heart. Pretreatment of the animals with 7-oxo-prostacyclin (PG12) 24–48 h prior to the experiment prevented fairly the Ca²⁺-depletion-induced depression in (Na,K)ATPase activity and the accompanying 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, 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 Ca²⁺-deprivation, the capability of heart sarcolemma to maintain sodium extrusion remains preserved, the expected aggravation of Ca²⁺-overload injury to Ca²⁺-paradox that would develop during Ca²⁺-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.