Correlations Between Na+-K+ATPase Activity and Acetylcholine Release in Rat Cortical Synaptosomes

Abstract

[³H]Acetylcholine efflux and Na⁺-K⁺ ATPase ion pump activity were measured concomitantly in rat cortical synaptosomes. Ouabain (500 μM), strophanthidin (500 μM). and parachloromercuribenzene sulfonate (500 μM) each inhibited ouabain-sensitive ⁸⁶Rb uptake and elevated [³H]acetylcholine release independently of the external calcium concentration. Veratridine (10 μM), electrical field stimulation (60 V, 60 Hz, 5-ms pulse duration), or the calcium ionophore A23187 (10μg/ml) also inhibited ouabain-sensitive ⁸⁶Rb uptake and released [³H]acetylcholine, but via a calcium-dependent process. Veratridine-induced [³H]acetylcholine release and ion pump inhibition were correlated over a wide range of drug concentrations and both effects were blocked by pre-treatment with tetrodotoxin (1 μM). The rate of [³H]acetyl-choline efflux from superfused synaptosomes was increased within 15 s of exposure to ouabain, strophanthidin, veratridine, A23187, or field stimulation, while ouabain-sensitive ⁸⁶Rb uptake was significantly decreased within a similar interval. These results suggest that [³H]acetylcholine release is due at least in part to inhibition of Na⁺-K⁺ ATPase.