Potentiation of potassium-evoked noradrenaline and neuropeptide Y co-release by cardiac energy depletion: role of calcium channels and sodium-proton exchange.
The role of the cardiac energy status in the potassium-evoked exocytosis of both noradrenaline and the sympathetic co-transmitter neuropeptide Y (NPY) was investigated in the guinea-pig perfused heart. The transmitter release was stimulated by potassium depolarization (10-80 mmol/l) during normoxic perfusion (pO2 > 100 mmHg) in the presence of glucose (11 mmol/l) and at various periods (5-40 min) of cardiac energy depletion. Energy depletion was induced either by anoxia (pO2 < 5 mmHg) or by cyanide intoxication (1 mmol/l), both in combination with glucose-free perfusion. Endogenous noradrenaline and NPY were determined in the coronary venous overflow by high-pressure liquid chromatography combined with electrochemical detection and by radioimmunoassay, respectively. Under normoxic conditions potassium depolarization evoked a co-release of both transmitters [molar ratio 862 (noradrenaline):1 (NPY)] at a threshold concentration of 40 mmol/l potassium. This transmitter overflow was characterized by its dependence on extracellular calcium and calcium influx through voltage-dependent neuronal calcium channels of the N-type. Cardiac energy depletion was accompanied by an acceleration and an enhancement of the potassium-evoked transmitter overflow. In comparison to normoxia, a 10-fold increased transmitter overflow with a comparable molar ratio [709 (noradrenaline:1 (NPY)] was evoked by 40 mmol/l potassium after 10 min of either anoxia or cyanide intoxication. This sensitization to potassium depolarization reached a peak after 10 min of energy depletion and was characterized by a markedly reduced threshold concentration (10 mmol/l potassium).(ABSTRACT TRUNCATED AT 250 WORDS)
Haass
M
M
Department of Cardiology, University of Heidelberg, Federal Republic of Germany.
Richardt
G
G
Schömig
A
A
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D003891:Desipramine / Q000494:pharmacology; D004734:Energy Metabolism; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009478:Neuropeptide Y / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism*
D015220:Calcium Channels; D009478:Neuropeptide Y; D012964:Sodium; D011188:Potassium; D003891:Desipramine; D009638:Norepinephrine