The depolarizing action of acetylcholine or carbachol in intestinal smooth muscle

1. The membrane potential of the longitudinal muscle of the guinea-pig ileum was recorded intracellularly with glass micro-electrodes.2. Acetylcholine or carbachol depolarized the membrane. The depolarization produced by 1.4 x 10(-6)M carbachol was only 3.6 mV less than that produced by 5.5 x 10(-5)M.3. When the change in size of the electrotonic potential was used to estimate the increase in membrane conductance produced by different concentrations of carbachol, the increase in conductance was about tenfold at 1.4 x 10(-6)M and about 100-fold at 5.5 x 10(-5)M. There was a significant (P < 0.025) regression of the change in size of the electrotonic potential on the logarithm of the concentration of carbachol over this dose range. This and other observations suggest that it is not the availability of receptors which curtails the depolarization produced by concentrations of carbachol in excess of 1.4 x 10(-6)M.4. Reducing the external sodium concentration shifted the level of peak depolarization produced by carbachol negatively, and increasing the external sodium concentration shifted it positively.5. Reducing the external chloride from 134 to 13 mM had no significant effect on the level of peak depolarization produced by carbachol. Reducing the external chloride to 7 mM shifted the level of peak depolarization 3.1 mV in a positive direction.6. Increasing the external potassium concentration had little effect on the level of peak depolarization produced by carbachol, and decreasing the external potassium shifted the level of peak depolarization positively.7. It was possible to account for the observed relationship between membrane potential and membrane conductance if the assumption was made that carbachol opens additional ion channels in the membrane which have an equilibrium potential of about -9 mV. It is suggested therefore that the depolarizing action of carbachol on this smooth muscle is limited by its equilibrium potential, and that the equilibrium potential and the membrane potential in the presence of large concentrations of carbachol (e.g. 5.5 x 10(-5)M) are very close. Hence changes in the level of peak depolarization produced by varying the ionic composition of the external solution probably reflect changes in the equilibrium potential fairly closely.8. A simple model in which carbachol opens conductances to sodium, potassium and chloride ions and in which these conductances are independent of external ion concentrations (and voltage) could account for the effects on the equilibrium potential of varying [Na(+)](0) and [Cl(-)](0) but not [K(+)](0).9. It is suggested that carbachol increases the conductance to sodium, potassium and possibly other cations, and that, if it increases chloride conductance, then the increase produced is small relative to the increase in conductance to cations.