Termination of transmitter release by stimulation of sodium-potassium activated ATPase.

Abstract

The release of acetylcholine (ACh) from Auerbach''s plexus of guinea-pig ileum was measured in eserinized Krebs solution using longitudinal muscle strip preparations. Removal of the external K+ enhanced the resting and stimulated release of ACh from the plexus. This effect was not affected by tetrodotoxin. On readmission of K+ to tissues which were suspended in K-free Krebs solution the release of ACh was promptly duced in both stimulated and unstimulated tissues. The extent of the reduction of ACh release depended on the exposure time to K-free solution, the recovery being delayed by longer exposure. The ACh releasing effect of 1,1-dimethyl-4-phenyl-piperazinium iodide (DMPP) was completely inhibited by the readmission of K+ to tissue which was kept in K-free Krebs solution. Rb+ substitution for K+ produced no change in ACh release and addition of 5.9 mM-Rb after K removal reduced the release of ACh as K did readmission. When the K+ were substituted by Cs+, the resting and stimulated release were enhanced. The amount of ACh released by a stimulus was enhanced at low and high frequency of sustained stimulation. Removal of the external K+ increased the release of tritiated noradrenaline (NA) [norepinephrine], from isolated rat iris; when K+ (5.9 mM) was readmitted, the release was reduced even below the control value. The stimulation of (Na+-K+)-activated ATPase in the membrane inhibits the release of transmitter, and under physiological condition Ca-fluxes and the subsequent inhibition of membrane ATPase may be involved in triggering the release of transmitter.