Effects of gap junction inhibition on contraction waves in the murine small intestine in relation to coupled oscillator theory

Abstract

Waves of contraction in the small intestine correlate with slow waves generated by the myenteric network of interstitial cells of Cajal. Coupled oscillator theory has been used to explain steplike gradients in the frequency (frequency plateaux) of contraction waves along the length of the small intestine. Inhibition of gap junction coupling between oscillators should lead to predictable effects on these plateaux and the wave dislocation (wave drop) phenomena associated with their boundaries. It is these predictions that we wished to test. We used a novel multicamera diameter-mapping system to measure contraction along 25- to 30-cm lengths of murine small intestine. There were typically two to three plateaux per length of intestine. Dislocations could be limited to the wavefronts immediately about the terminated wave, giving the appearance of a three-pronged fork, i.e., a fork dislocation; additionally, localized decreases in velocity developed across a number of wavefronts, ending with the terminated wave, which could appear as a fork, i.e., slip dislocations. The gap junction inhibitor carbenoxolone increased the number of plateaux and dislocations and decreased contraction wave velocity. In some cases, the usual frequency gradient was reversed, with a plateau at a higher frequency than its proximal neighbor; thus fork dislocations were inverted, and the direction of propagation was reversed. Heptanol had no effect on the frequency or velocity of contractions but did reduce their amplitude. To understand intestinal motor patterns, the pacemaker network of the interstitial cells of Cajal is best evaluated as a system of coupled oscillators.

Haustral boundary contractions in the proximal 3-taeniated rabbit colon

“…In the present study, the distal side of the plateau always had a higher frequency, indicating that the highest intrinsic frequency is in the distal colon, which was also noted in previous studies (51,56,58). The ripple maps also show frequently changing direction of propagation, which can be explained by the emergence of multiple pacemakers (43) or it may suggest limited coupling between weakly coupled oscillators (45).…”

“…7 from a study by Dinning et al (13). Dislocations are seen at the end of a frequency plateau where a wave is lost when the coupling is not strong enough to overcome the frequency difference at that point (45). In the present study, the distal side of the plateau always had a higher frequency, indicating that the highest intrinsic frequency is in the distal colon, which was also noted in previous studies (51,56,58).…”

“…Annihilation takes place when the propagating events occur within the same physical structure and are followed by a refractory period, as happens with nerve action potentials, slow waves, and forest fires. Annihilation is well known to take place with motor patterns that are driven by an interstitial cells of Cajal (ICC) network (35,42,45).…”

“…A coupled oscillator system with a frequency gradient is assumed to be underlying the ripple motor pattern. At a certain point, the coupling is not strong enough to overcome the difference in intrinsic frequency and dislocations occur (45). ified activity is summed with the haustral boundary pacemaker to obtain the predicted activity occurring in the musculature.…”

Induction of rhythmic transient depolarizations associated with waxing and waning of slow wave activity in intestinal smooth muscle

“…Diamant and Bortoff (6) originally presented the hypothesis that waxing and waning resulted from the interaction of two high-frequency pacemakers of slightly different frequencies. This, indeed, occurs at the plateau boundaries of a system of coupled oscillators exhibiting a frequency gradient (21).…”