Status of Ca(2+)-channels in hearts perfused with Ca(2+)-free medium as well as upon reperfusion (Ca(2+)-paradox).
Although a wide variety of biochemical changes have been observed during the occurrence of Ca(2+)-paradox, very little is known about membrane alterations during Ca(2+)-free perfusion which may predispose the heart to the development of intracellular Ca(2+)-overload in the Ca(2+)-paradox phenomenon. In view of the marked influx of Ca2+ into the myocardial cell during Ca(2+)-paradox and the involvement of Ca(2+)-channels in the entry of Ca2+, we determined the status of Ca(2+)-channels by measuring the binding of a Ca(2+)-antagonist, [3H] PN200-110, with membranes obtained from rat hearts perfused with Ca(2+)-free medium. The density of Ca(2+)-channels in the membranes was increased upon perfusing the heart with Ca(2+)-free medium for > 2 min or when the perfusion medium contained less than 25 microM concentration of Ca2+. The increase in Ca(2+)-channel density was attenuated when the hearts were perfused with Ca(2+)-free medium in the presence of a low concentration (35 mM) of Na+ or at low temperature (21 degrees C); two conditions which are known to prevent the occurrence of Ca(2+)-paradox. These results indicate that increased density of Ca(2+)-channels due to Ca(2+)-free perfusion may contribute towards the massive Ca(2+)-influx into the myocardial cell for the induction of intracellular Ca(2+)-overload associated with Ca(2+)-paradox during reperfusion with Ca(2+)-containing medium.
Persad
S
S
Division of Cardiovascular Sciences, St Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada.
Gupta
K K
KK
Dhalla
N S
NS
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism / Q000502:physiology*; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D003600:Cytosol / Q000378:metabolism; D003840:Deoxycholic Acid / Q000494:pharmacology; D006321:Heart / Q000502:physiology*; D066298:In Vitro Techniques; D017275:Isradipine / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009200:Myocardial Contraction; D015425:Myocardial Reperfusion; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D015220:Calcium Channels; D003840:Deoxycholic Acid; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium; D017275:Isradipine