Slow wave propagation and plasticity of interstitial cells of Cajal in the small intestine of diabetic rats

Abstract

The number of myenteric interstitial cells of Cajal (ICC-MY), responsible for the generation and propagation of the slow wave in the small intestine, has been shown to decrease in diabetes, suggesting impairment of slow-wave (SW) propagation and related motility. To date, however, this expected decrease in SW propagation has neither been recorded nor analysed. Eleven rats were treated with streptozotocin and housed in pairs with 11 age-matched control animals. After 3 or 7 months, segments of duodenum, jejunum and ileum were isolated and divided into two parts. One part was processed for immediate freezing, cryosectioning and immunoprobing using anti-c-Kit antibody to quantify ICC-MY. The second part was superfused in a tissue bath, and SW propagation was recorded with 121 extracellular electrodes. In addition, a cellular automaton was developed to study the effects of increasing the number of inactive cells on overall propagation. The number of ICC-MY was significantly reduced after 3 months of diabetes, but rebounded to control levels after 7 months of diabetes. Slow-wave frequencies, velocities and extracellular amplitudes were unchanged at any stage of diabetes. The cellular automaton showed that SW velocity was not linearly related to the number of inactive cells. The depletion of ICC-MY is not as severe as is often assumed and in fact may rebound after some time. In addition, at least in the streptozotocin model, the initial reduction in ICC-MY is not enough to affect SW propagation. Diabetic intestinal dysfunction may therefore be more affected by impairments of other systems, such as the enteric system or the muscle cells.

Functional reentry and circus movement arrhythmias in the small intestine of normal and diabetic rats

“…The purpose of that study was to correlate the expected decrease in slow wave propagation with the reported decrease in the census of ICC-MY in the small intestine (8,10,20,30). To our initial surprise, we did not measure a significant decrease in slow wave propagation although there was a reduction in the number of ICC-MY by ϳ50% (10).…”

“…Animal preparations, electrical recordings, and data analysis were presented previously in detail (10). In brief, 11 male young adult Wistar rats were treated with an intraperitoneal injection of STZ at 60 mg/kg and housed together with 11 age-matched control rats.…”

“…In ϳ15% of the segments, slow wave propagation did not originate from one or a few foci (10,11). Instead, the slow wave was seen to propagate in a circular fashion for relatively long periods of time, whereby the impulse could rotate in either a clockwise or an anticlockwise direction.…”

Furthering the debate on the role of interstitial cells of Cajal in enteric inhibitory neuromuscular neurotransmission

“…Careful reexamination of observations shall provide the next steps for understanding pathophysiology. For example, there is loss of ICCs in diabetes mellitus, but after a period, these cells may grow back (22). Given the intrinsic ability of ICCs to respond to stem cell factor, multicellular apoptosis in the gut wall in diabetes (9,22), as well as regenerative responses (22), merits aggressive examination.…”

“…For example, there is loss of ICCs in diabetes mellitus, but after a period, these cells may grow back (22). Given the intrinsic ability of ICCs to respond to stem cell factor, multicellular apoptosis in the gut wall in diabetes (9,22), as well as regenerative responses (22), merits aggressive examination. Arguments should rise above semantic reconciliation and be directed at dissecting pathophysiology of gastrointestinal motility disorders to expand the currently limited therapeutic options.…”