The nature of noncholinergic membrane potential responses to transmural stimulation in guinea pig ileum.

The effect of substance P antagonism on membrane potential responses to transmural nerve stimulation in the presence of atropine was examined in circular smooth muscle of the guinea pig ileum. Intracellular recordings of membrane potential responses recorded 3-5 mm oral to the transmural stimulus consisted of an inhibitory junction potential followed by two distinct depolarizations referred to as early and late excitatory junction potentials. Substance P antagonism was achieved by desensitization with high doses of substance P or use of the antagonist Spantide (Sigma Chemical Co., St. Louis, MO). Substance P antagonism had no effect on the amplitude of the inhibitory junction potential, caused an increase in the latter portion of the early excitatory junction potential, and abolished the late excitatory junction potential. The excitatory junction potential potentiated by substance P receptor antagonism was associated with a decrease in membrane resistance, increased in amplitude with conditioning hyperpolarizations to the estimated equilibrium potential for K+, and was blocked by the Cl-/HCO3- exchange inhibitor DIDS or prolonged perfusion with low-chloride solution. These studies suggest that a noncholinergic, non-substance P neurotransmitter is released from enteric motoneurons that produces excitation through an increase in smooth muscle chloride conductance.