Ion dependence of the release of noradrenaline by tetraethylammonium and 4‐aminopyridine from cat splenic slices

Abstract

1 Cat splenic slices prelabelled with [3H]-noradrenaline were incubated in oxygenated Krebsbicarbonate solution at 37°C, and the spontaneous total 3H release into different incubation media monitored. In normal Krebs bicarbonate solution, the spontaneous tritium fractional release amounted to 3.7% of the tissue radiactivity content per 5 min collection period. 2 Tetraethylammonium (TEA) increased spontaneous transmitter release in a concentrationdependent manner; the release was maximal at 30 mM and was 3.5 times the basal release. 3 4-Aminopyridine (4-AP) also enhanced the spontaneous release of tritium. The response increased linearly with 4-AP concentration (1-10 mM). With 10 mM 4-AP, the release was as much as 6 times the basal transmitter release. Guanidine was much less potent than either TEA or 4-AP. 4 The secretory response to TEA or 4-AP was little affected by changes in external Ca2", Mg2+, Na+, Cl-, H2PO4 or by tetrodotoxin. 5 However, transmitter release evoked by TEA or 4-AP strongly depended upon the concentration of HCO3-of the incubation solution; in fact, the secretory response varied almost linearly between I and 25 mM HCO3 . 6 The mechanisms underlying these effects are probably related to the well-known ability ofTEA and 4-AP to block K+ conductance that would cause depolarization of the splenic sympathetic nerve terminals. The HCO3-requirements for the secretory response are probably related to the ability of C02/HCO3-solutions to mobilize and release Ca2+ from intracellular organelles.

Multiple effects of 4-aminopyridine on feline and rabbit sinoatrial node myocytes and multicellular preparations

“…However, it has been previously found that in perfused cat spleen, 4-AP at high concentrations (>3 mM) induced spontaneous release of NA [8]. In cat splenic slices, the increase in spontaneous NA release induced by 4-AP (1-10 mM) was insensitive to TTX, 1 µM, both in 2.5 and 0 mM Ca 2+ solution [23].…”