Indirect effects of acetylcholine on the electrogenic sodium pump in bull-frog atrial muscle fibres.

1. Effects of acetylcholine (ACh) on the activity of electrogenic Na+ pump in bullfrog atrial muscle fibres were examined using the single sucrose-gap voltage clamp technique. 2. In the K+-free solution, 10 microM-ACh induced a large outward current (ACh-induced current) with an increase in the membrane conductance. 3. The amplitude of the ACh-induced current decreased to 15% of the control 10 min after application of 1 microM-ouabain, suggesting the contribution of electrogenic Na+ pump to the ACh-induced current. The remaining ACh-induced current was not affected even if the concentration of ouabain was increased ten times. 4. The K+-activated current induced by an activation of the electrogenic Na+ pump was suppressed or reversed its direction during the course of the ACh-induced current. 5. The ACh-induced current was completely inhibited by applications of either atropine or barium ions while the K+-activated current was not affected. 6. Both ouabain-sensitive and -insensitive ACh-induced currents were decreased when the membrane was hyperpolarized and eliminated around -95 mV. 7. The ouabain-sensitive component was decreased by increasing the external K+ concentration [K+]o; the proportions of this current to ACh-induced current in 0.5, 0.75, 1 and 2 mM [K+]o were 54, 42, 34 and 14%, respectively. 8. The current-voltage (i-v) relation obtained in 2 or 4 mM [K+]o, where the currents carried by Na+ and Ca2+ were blocked by application of 1 microM-TTX and 1 mM-Cd2+, exhibits marked inward-going rectification but does not show a clear N-shaped feature. Ba2+ (1 mM) induced an inward current at the holding potential (-80 mV) and eliminated the inward-going rectification of the membrane. 9. These results suggest that the increase in the K+ permeability by ACh increases the concentration of K+ immediately outside of the membrane, which in turn stimulates the electrogenic Na+ pump mechanism. The physiological significance of the action of ACh on the electrogenic Na+ pump in bull-frog atrium is discussed in relation to the background K+ current (IK,1).