On the Nature of the Oscillations of the Membrane Potential (slow Waves) Produced by Acetylcholine or Carbachol in Intestinal Smooth Muscle

1. Intracellular recording was made with glass micro-electrodes from cells of the longitudinal muscle of the guinea-pig ileum in isotonic and in hypertonic solution.2. In isotonic solution spontaneous bursts of electrical activity occurred; these consisted of a slow potential component which carried a burst of spike action potentials. Acetylcholine increased the size (and the frequency) of the slow potential component. This had the effect of first reducing and then abolishing the spike potentials; continuous slow wave activity was thus produced. Slow waves were about 1 sec in duration and up to 50 mV in size in isotonic solution.3. In hypertonic solution the membrane potential was stable. There were no spontaneous spikes and no slow potentials. However, spikes, but not slow potentials, were elicited by depolarizing current. Carbachol (or acetylcholine) reduced the membrane potential and initiated spikes and oscillations of the membrane potential (slow waves). Slow waves were 2-5 sec in duration and 10-40 mV in size in hypertonic solution.4. The response to carbachol in hypertonic solution was unaffected by surgical denervation of the tissue, by tetrodotoxin, or by ganglion blocking agents, indicating that muscarinic stimulants produced their effects by acting directly on the smooth muscle cell.5. In hypertonic solution slow waves occurred only in the presence of a muscarinic stimulant and could not be elicited with depolarizing current (unless carbachol was present) nor by increasing the external potassium concentration.6. In hypertonic solution slow waves were abolished by hyperpolarizing the membrane and their rate of rise was proportional to the level of the membrane potential from which they arose. The membrane resistance was reduced at the peak of the slow wave. Slow waves were rapidly abolished by sodium-deficient solutions but spikes were not.7. It is suggested that slow waves represent an inward current through a slow, sodium-sensitive and voltage-dependent ion channel, and that acetylcholine or carbachol increase, while hypertonic solution decreases, the current carried by this channel.