Cholinergic stimulation activates a non-selective cation current in canine pyloric circular muscle cells

1. Cholinergic stimulation of circular muscle from the canine pyloric sphincter results in excitatory junction potentials and an increase in slow-wave frequency. Experiments were performed on isolated pyloric muscle cells to determine the effects of acetylcholine on membrane conductance and voltage-dependent ionic currents. 2. Acetylcholine depolarized circular muscle cells and increased membrane conductance. Under voltage clamp, these effects were associated with the development of an inward current. 3. The ACh-dependent current (IACh) reversed at about -20 mV and was about equally selective for potassium and sodium. Changes in the chloride gradient had no effect on the reversal potential of IACh. 4. The response to ACh was blocked by atropine suggesting that the response was mediated by muscarinic receptors. IACh could not be elicited in the presence of ions normally used to block potassium currents (e.g. bath-applied TEA+ and replacement of Ki+ with Csi+. 5. In some cells single-channel openings could be resolved in response to ACh. These channels had a slope conductance of 30 pS, and open probability increased with depolarization. 6. Acetylcholine had little or no effect on voltage-dependent Ca2+ currents, and increased voltage-dependent outward currents. The latter effect may have been due to increased release of Ca2+ from internal stores. 7. The non-selective cationic current elicited by ACh can explain the excitatory junction potentials in pyloric muscle cells that are generated by transmural nerve stimulation and may also explain the chronotropic effects of ACh on slow waves.