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

Abstract

Cannon described in 1902 the segmentation motor activity of the small intestine (Canon WB. J Med Res 7: 72-75, 1902). This motor pattern can arise when low-frequency transient depolarizations are evoked in the interstitial cells of Cajal associated with the deep muscular plexus (ICC-DMP) network, which then affect the omnipresent slow wave activity: changing its regular amplitude into a waxing and waning pattern. The objective of the present study was to investigate physiological stimuli that could induce the low-frequency component. Intracellular recordings were obtained from circular muscle with or without attached mucosa. Decanoic acid (1 mM) and butyric acid (10 mM) both evoked low-frequency transient depolarizations but through different mechanisms. Decanoic acid-induced waxing and waning was initiated by purely myogenic means when perfused onto exposed circular muscle. Butyric acid required the intact mucosa and uninhibited neural activity to elicit the low-frequency response. Evidence is provided that the transient rhythmic depolarizations occur in the absence of interstitial cells of Cajal associated with the myenteric plexus (ICC-MP). Onset of the slow transient depolarizations was stimulated by addition of N(ω)-nitro-l-arginine (l-NNA; 100 μM); thus the low-frequency component seems to be under chronic inhibition by nitric oxide. Excitatory tachykinergic stimulation induced the low-frequency component since substance P (0.5 μM) evoked it in the presence of neural blockade. In summary, interplay between two networks of myogenic pacemakers, neural activity, and nutrient factors such as fatty acids plays a role in the generation of the rhythmic low-frequency component that is essential for the development of the checkered segmentation motor pattern.

Neurotensin Changes Propulsive Activity into a Segmental Motor Pattern in the Rat Colon

“…In the small intestine, the classical segmentation motor activity is generated when the ICC associated with the deep muscular plexus (ICC-DMP) produce a stimulus-dependent rhythmic electrical activity. 34,35 In the rat colon, it is the ICC-MP that generates a stimulus-dependent low frequency activity; the laboratories of Jimenez in the rat 31 and Takaki in the mouse 36 showed that ICC-MP are associated with a low frequency pacemaker that can drive contractions at frequencies from 0.3 to 2 cpm, 19,21,22,[31][32][33] hence the on/off pattern observed in the present study is likely to be associated with pacemaking from the ICC-MP. It is not known where the ultra-slow pacemaker that drives the slow propagating segmental contractions is located; it may be within the ENS or in the intramuscular ICC (ICC-IM).…”

“…We have shown that substance P can evoke the ICC-DMP pacemaker. 43 Potential stimuli are not limited to neurotransmitters; fatty acids such as butyrate and decanoic acid can also evoke the low frequency pacemaker activity, 34 and so can distention. 44 Siegle and Ehrlein's observation that neurotensin can evoke segmentation can be explained by the induction of ICC-DMP pacemaker activity.…”

Stimulus‐induced pacemaker activity in interstitial cells of Cajal associated with the deep muscular plexus of the small intestine

“…4Ba, shows a waxing and waning pattern which has been extensively described elsewhere. 22 A CWT time-frequency plot indicated that this pattern was composed of two different frequency signals, 2 and 28 cpm (Fig. 4Bb).…”

“…With ICC-MP present, slow wave activity was recorded at 15-28 cpm (21.1 AE 4.3 cpm; n = 15) as shown previously. 2,21,22 In addition, we recorded two types of electrical activities that included a low frequency component when recorded close to the ICC-DMP. Fig.…”

Ageing and Gastrointestinal Sensory Function

“…But in that case, the maximum amplitude becomes twice the original amplitude. When we confi rmed the induction of waxing and waning by intracellular recording of the electrical activity, no change in maximum slow wave amplitude occurred (Pawelka and Huizinga 2015 ). Suzuki deduced the existence of two prominent similar frequencies in the waxing and waning pattern based on FFT analysis but FFT might not be the best method to evaluate frequencies in a signal that changes markedly over time.…”