Effect of tetraethylammonium on noradrenaline release from cat spleen treated with tetrodotoxin

Abstract

EXPERIMENTS by Katz and Miledi¹ on the giant synapse of the squid stellate ganglion pretreated externally with tetrodotoxin (TTX) to block the conducted nerve impulses, and internally with tetraethylammonium (TEA) to block the potassium current, showed that a local regenerative response confined to the presynaptic terminal was obtained on depolarisation, provided that the external calcium concentration was sufficiently high. Strontium and barium substituted for calcium, and manganese and magnesium reduced the regenerative response. TEA, in the presence of TTX, also caused a massive release of acetylcholine from the frog neuromuscular junction in response to a depolarisation of the motoneurone terminals². These results offered direct evidence for the existence in the nerve terminals of a TTX-resistant calcium channel involved in transmitter release, and suggested that TEA, by allowing an inward calcium current to become regenerative, enhanced transmitter release. The release of noradrenaline (NA) from sympathetic nerves also requires calcium, and further, strontium and barium substitute for calcium in sustaining release, and magnesium, manganese and lanthanum block release³. Moreover, TEA has also been shown to enhance NA release after electrical stimulation of sympathetic nerves^4–6. These observations suggest that a calcium channel also exists in the sympathetic nerve terminals and is responsible for the release of NA. The present investigation was undertaken to determine if in the presence of TEA and TTX, depolarisation of the sympathetic nerve terminal initiates a ‘regenerative’ inward calcium current which leads to an explosive release of NA. We report that it does.