Effects of intracellular Ca2+ chelating on noradrenaline release in normoxic and anoxic hearts.
1. Ischaemia and anoxia induce excessive noradrenaline (NA) release in the heart by a mechanism independent of both nerve activity and extracellular Ca2+. The present study was designed to examine the potential role of intracellular Ca2+ mobilization in anoxic NA release in the heart by chelating intracellular free Ca2+. 2. In normoxic hearts, preloading with an intracellular free Ca2+ chelator (BAPTA) reduced neuronal NA release by 65%, confirming the effectiveness of the loading protocol. Release of NA independent of nerve activity occurred in hearts subjected to a 40 min period of anoxic, substrate-free and nominal Ca(2+)-free perfusion. Loading hearts with BAPTA prior to anoxia failed to reduce NA overflow (1561 +/- 147 vs 1496 +/- 206 pmol/g over 40 min). Infusion with BAPTA (20 mumol/L) during the first 25 min of the anoxic period reduced the quantity of anoxic NA release by approximately 25% from 2013 +/- 124 to 1476 +/- 207 pmol/g (P < 0.05). 3. Our results confirm that anoxic NA release is predominantly a Ca(2+)-independent process with Ca2+ mobilization from endogenous storage playing only a minor contributing role.
Du
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XJ
Alfred and Baker Medical Unit, Baker Medical Research Institute, Melbourne, Victoria, Australia. xiaojun.du@alice.baker.edu.au
Bobik
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Esler
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Dart
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D000818:Animals; D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D002614:Chelating Agents / Q000737:chemistry; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D004558:Electric Stimulation; D006321:Heart / Q000294:innervation; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D002614:Chelating Agents; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D010100:Oxygen; D002118:Calcium; D009638:Norepinephrine