Effect of tetraethylammonium and barium on the release of noradrenaline from the perfused cat spleen by nerve stimulation and potassium

Abstract

The effect of tetraethylammonium (TEA) and barium on release of noradrenaline (NA) from the cat spleen by nerve stimulation or potassium was investigated. In spleens perfused with normal Krebs solution, the NA output at 5 Hz was barely detectable, and the output at 30 Hz was about 5-fold greater than the output at 5 Hz. TEA (1 mM) or barium (2.5 mM) increased NA output at 5 Hz by 5-fold, but did not enhance it at 30 Hz. A maximal effect of TEA was obtained at about 1–3 mM. Enhancement of NA release by TEA was readily reversible. Output of NA induced by high potassium was not affected by TEA or barium. The effect of TEA on release was related to the external calcium concentration. Insignificant outputs obtained at 5 Hz in 0.1 and 0.5 mM calcium-Krebs solutions were markedly increased by TEA, and were 2- and 5-fold greater than the control output at 5 Hz in normal Krebs solution containing 2.5 mM calcium. TEA enhanced release at all calcium concentrations up to 5 mM, but maximum output was still obtained at 2.5 mM. Increasing the potassium concentrations of normal Krebs solution to 10, 15 and 20 mM depressed NA outputs at 5 Hz by 50, 55 and 75%, respectively. TEA (1 mM) partially antagonized the inhibitory effect of potassium on release, and in zero potassium-Krebs solution it increased output by about 50% over that obtained in normal Krebs solution. The ratio of NA outputs at 30 and 5 Hz during perfusion with Krebs solution containing TEA was about 0.6, and it approached the normal value as the calcium concentration of the perfusion medium was reduced. TEA facilitated release even at 30 Hz in low-calcium solutions. It is suggested that the enhancement of NA release by TEA and barium is due to the greater influx of calcium ions into the sympathetic nerves during the course of an action potential.