Evidence that substance P does not mediate slow synaptic excitation within the myenteric plexus

ELECTRICAL stimulation of presynaptic fibres to the so-called AH1 or type II2 myenteric neurones in guinea pig small intestine evokes a slow excitatory postsynaptic potential (e.p.s.p.) characterised by long-lasting depolarisation associated with increased membrane resistance and augmented excitability3. Two substances have been implicated as possible neurotrans-mitters for the slow e.p.s.p. Katayama and North reported that application of substance P to myenteric neurones mimicked the slow e.p.s.p.4, and J.D.W. and C.J.M. presented several lines of evidence for serotonin as the transmitter substance5,6. We now report that methysergide, a drug which abolishes both the slow e.p.s.p. and the action of exogenous serotonin5,6, does not affect the action of substance P on guinea pig myenteric neurones. The results suggest that substance P is unlikely to be the neuro-transmitter which mediates the slow e.p.s.p

An electrical description of the generation of slow waves in the antrum of the guinea-pig

This paper provides an electrical description of the generation of slow waves in the guinea-pig gastric antrum. A short segment of a circular smooth muscle bundle with an attached network of myenteric interstitial cells of Cajal (ICC-MY) and longitudinal muscle sheet was modelled as three electrical compartments with resistive connexions between the ICC-MY compartment and each of the smooth muscle compartments. The circular smooth muscle layer contains a proportion of intramuscular interstitial cells of Cajal (ICC-IM), responsible for the regenerative component of the slow wave. Hence the equivalent cell representing the circular muscle layer incorporated a mechanism, modelled as a two stage reaction, which produces an intracellular messenger. The first stage of the reaction is proposed to be activated in a voltage-dependent manner as described by Hodgkin and Huxley. A similar mechanism was incorporated into the equivalent cell describing the ICC-MY network. Spontaneous discrete transient depolarizations, termed unitary potentials, are detected in records taken from either bundles of circular smooth muscle containing ICC-IM or from ICC-MY. In the simulation the mean rate of discharge of unitary potentials was allowed to vary with the concentration of messenger according to a conventional dose–effect relationship. Such a mechanism, which describes regenerative potentials generated by the circular muscle layer, also simulated the plateau component of the pacemaker potential in the ICC-MY network. A voltage-sensitive membrane conductance was included in the ICC-MY compartment; this was used to describe the primary component of the pacemaker potential. The model generates a range of membrane potential changes with properties similar to those generated by the three cell types present in the intact tissue

Experimental basis for realistic large scale computer simulation of the enteric nervous system

1. The enteric nervous system is perhaps the most accessible part of the mammalian nervous system in which it is feasible to attempt large scale computer simulation that is based closely on experimentally determined data. Here we summarize the data obtained for simulation of motility reflexes in the guinea-pig small intestine. 2. The chemistry, morphology and connectivity of each type of neuron involved in intrinsic reflexes have been investigated and most classes of neurons are physiologically well characterized. This includes primary sensory neurons, ascending and descending interneurons and motor neurons to circular and longitudinal muscle. 3. The responses of primary sensory neurons and the physiology of synaptic transmission from sensory neurons to interneurons and motor neurons, from interneurons to interneurons and from interneurons to motor neurons have been recorded during reflexes and in some cases the pharmacology of transmission has also been investigated. 4. Computer simulation, in which the activities of up to 30,000 neurons are modelled, produces patterns of activity that closely mimic those recorded in physiological experiments