Enhancement of 3H-noradrenaline overflow from cardiac sympathetic nerves by low Ca and tetraethylammonium.

1. The influence of varying concentrations of Ca and tetraethylammonium (TEA) was investigated on spontaneous and stimulation-evoked overflow of 2H-noradrenaline in the isolated heart of the guinea pig. 2. Perfusion of the heart with Krebs-bicarbonate solution containing 0-2.5 mM Ca does not modify the spontaneous overflow of 3H-noradrenaline. 3. Exposure of the heart to 3, 10 or 30 mM TEA for 15 min had also no significant effect on the spontaneous overflow of 3H-noradrenaline. 4. A combination of low Ca (0.1-0.3 mM) and 10-30 mM TEA produced about 2- to 4-fold increase in the spontaneous overflow of 3H-noradrenaline. The response was reduced in 0 mM Ca plus 30 mM TEA. 5. 3H-noradrenaline overflow induced by 0.25 mM Ca and 30 mM TEA was abolished by prior treatment of the heart with 0.3 microM tetrodotoxin (TTX). Washout of TTX restored the response. 6. 3H-noradrenaline overflow induced by low Ca and high TEA was depressed in the presence of 15 mM Mg or 1 mM lanthanum. 7. Stimulation-evoked (1 Hz for 180s) 3H-noradrenaline overflow was abolished in 0.1 mM Ca medium. However, addition of 30 mM TEA to such medium not only doubled spontaneous overflow, but also that evoked by electrical stimulation was greatly facilitated (about 4-fold). 8. It is implied that sympathetic nerves develop spontaneous action potentials in low Ca medium, but not enough Ca enters to produce an overflow of 3H-noradrenaline. However, upon exposure to TEA, the duration of spontaneous action potentials is prolonged. As a result, enough Ca enters into the neurone to produce exocytotic release of 3H-noradrenaline even in the absence of electrical stimulation.