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).