An analysis of inhibitory junction potentials in the guinea-pig proximal colon.

Intracellular recordings were made from either sheets or isolated bundles of the circular muscle layer of guinea-pig proximal colon and the responses evoked by stimulating inhibitory nerve fibres were analysed. Inhibitory junction potentials (IJPs), evoked by single stimuli, had two components which could be separated on their pharmacological and temporal characteristics and their voltage sensitivities. The initial component, which was abolished by apamin and reduced in amplitude by pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), had a brief time course: its amplitude was changed when the external concentration of potassium ions ([K+](o)) was changed. The second component of the IJP had a slower onset than the first component, was abolished by l-nitroarginine (NOLA) and oxadiazolo quinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase: its amplitude was little affected by changing [K+](o) and was increased when the membrane potential of the circular layer was hyperpolarized. The observations suggest that the initial component of the IJP results from the release of ATP which triggers an increase in membrane conductance to K+ and that the second component results from the release of nitric oxide which suppresses a background inward current.

Murine intestinal migrating motor complexes: longitudinal components.

Spontaneous migrating contractions have been described in the circular muscle of the isolated mouse colon and terminal ileum, however, spontaneous events equivalent to these have not been reported in the longitudinal muscle. The longitudinal muscle shortenings in the colon and ileum, which are of similar form, frequency and pharmacology to the circular muscle colonic and ileal migrating motor complexes (CMMCs and IMMCs), are recorded in the present study. The spontaneous ileal and colonic longitudinal muscle shortenings appear to be neurally organized as they are abolished by tetrodotoxin (1 micro mol L-1), hexamethonium (500 micro mol L-1) and morphine (1 micro mol L-1). Endogenously released nitric oxide slowed the frequency of spontaneous ileal and colonic longitudinal muscle shortenings and 5-hydroxytryptamine increased their frequency. Hyoscine (1 micro mol L-1) abolished longitudinal shortenings in the ileum and reduced the amplitude of longitudinal shortening by approximately 44% in the colon. Shortenings were effectively abolished by nifedipine (1 micro mol L-1). Surgical sectioning of the colon identified that each region of the colon contracted longitudinally in an independent fashion; the distal colon contracted to the greatest amplitude and lowest frequency. The longitudinal preparation is suitable to initially assess the actions of novel pharmacological agents on spontaneous, neurally coordinated, CMMCs and IMMCs in emptied isolated murine intestines.

Motility in the isolated mouse colon: migrating motor complexes, myoelectric complexes and pressure waves.

This study has used mechanical, together with pressure/volume recordings or electrophysiological recordings, to investigate the spontaneous activity in isolated preparations of mouse colon. In the former preparations, when not distended with fluid, spontaneous colonic migrating motor complexes (CMMCs) were observed using isotonic transducers. When the colons were distended with fluid, CMMCs continued at an increased frequency and in addition were associated temporally, with rises in intraluminal pressure and pulses of distally ejected fluid. 5-Hydroxytryptamine (1 micro mol L-1) or NG-nitro-l-arginine (100 micro mol L-1) increased the frequency of propulsive activity and this activity was abolished by hexamethonium (500 micro mol L-1). In a second preparation, myoelectric complexes recorded from circular muscle cells in colons using intracellular microelectrodes, were found to correlate in frequency and phase with CMMCs. The experiments indicate that CMMCs are intimately related to pressure waves in the fluid-filled viscus and the muscle membrane potential changes that have been recorded during myoelectric complexes are likely to be analogous to those occurring during fluid-filled propulsive activity.

Neural integrity is essential for the propagation of colonic migrating motor complexes in the mouse.

The mechanisms that underlie the propagation of contractions along the colon are uncertain. We have examined whether spontaneous colonic migrating motor complexes (CMMCs) migrate through a region of muscle paralysis, or through a region where neural transmission was disrupted in the isolated mouse colon. Mouse colon was mounted in a separately perfused three-compartment organ bath and recordings of circular muscle tension were made. Drug application was restricted to the middle compartment. Application of nifedipine (1 micromol L(-1)), an l-type calcium channel antagonist, reduced the contraction amplitude by approximately 94%, without affecting the form of contractions in the proximal and distal compartments. Moreover, CMMCs appeared to remain temporally related in all compartments. In contrast, interruption of neural transmission in the middle compartment by either tetrodotoxin (1.6 micromol L(-1)), hexamethonium (500 micromol L(-1)) or a low-calcium, high-magnesium solution abolished CMMCs in this compartment; contractions recorded in the proximal and distal compartments became slower in frequency and were no longer synchronized. The experiments suggest that there may be more than one 'pacemaker' generating spontaneous CMMCs and that CMMCs can migrate through a region where there is minimal tension generation, but not through a region where neural integrity has been compromised.