Interstitial cells of Cajal mediate mechanosensitive responses in the stomach

Abstract

Changes in motor activity are a basic response to filling of smooth muscle organs. Responses to gastric filling, for example, are thought to be regulated by neural reflexes. Here, we demonstrate a previously uncharacterized aspect of stretch-dependent responses in visceral smooth muscles that is mediated by mechanosensitive interstitial cells of Cajal. Length ramps were applied to the murine antral muscles while recording intracellular electrical activity and isometric force. Stretching muscles by an average of 27 ؎ 1% of resting length resulted in 5 mN of force. Increasing length caused membrane depolarization and increased slow-wave frequency. The responses were dependent on the rate of stretch. Stretch-dependent responses were not inhibited by neuronal antagonists or nifedipine. Increases in slow-wave frequency, but not membrane depolarization, were inhibited by reducing external Ca 2؉ (100 M) and by Ni 2؉ (250 M). Responses to stretch were inhibited by indomethacin (1 M) and were absent in cyclooxygenase II-deficient mice, suggesting that cyclooxygenase II-derived eicosanoids may mediate these responses. Dual microelectrode impalements of muscle cells within the corpus and antrum showed that stretch-induced changes in slow-wave frequency uncoupled proximal-to-distal propagation of slow waves. This uncoupling could interfere with gastric peristalsis and impede gastric emptying. Stretch of antral muscles of W͞W V mice, which lack intramuscular interstitial cells of Cajal, did not affect membrane depolarization or slow-wave frequency. These data demonstrate a previously uncharacterized nonneural stretch reflex in gastric muscles and provide physiological evidence demonstrating a mechanosensitive role for interstitial cells of Cajal in smooth muscle tissues.gastric compliance ͉ pacemaker ͉ stretch ͉ slow waves ͉ propagation

Control of Urinary Drainage and Voiding

“…In the last decade, these have been identified as bladder ICCs (BICCs) and the emerging consensus is that they are likely to play an important role in modulating bladder motility (74)(75)(76)(77)(78)(79)(80)(81). ICCs were first identified in the gastrointestinal tract where they function as pacemakers, neuron transducers, and mechanosensors to modulate smooth muscle motility (82)(83)(84)(85), and more than a dozen gut disorders are linked to ICC dysfunction, including gastroparesis and intestinal pseudo-obstruction (86,87). In urinary bladder, much less is understood.…”

Toward a Concept of Stretch Coupling in Smooth Muscle: A Thesis by Lars Thuneberg on Contractile Activity in Neonatal Interstitial Cells of Cajal

“…Different thresholds (ICC<LM<CM) make lots of sense, if you consider the ICC the alarm-clocks, and the work-load on the longitudinal muscle being more related to moving along and mixing the more fluid surface contents, while the hard work of the circular muscle is called upon, when it has to produce occluding contractions against a semi-solid content, as in segmentation motility! The notion that ICC may be stretch sensors has been proposed by others as well (Gabella, 1979;Rumessen et al, 1982;Fox et al, 2000;Won et al, 2005). That distention may be followed by peg and socket junctions has been explained in the previous paper (Thuneberg and Peters, 2001).…”

The effect of extracorporeal shock wave lithotripsy on distribution of interstitialcells of Cajal in rabbit renal pelvis and proximal ureter

“…Some pacemaker potentials were able to be shown by electrophysiological studies in the renal pelvis in animal studies (6,14). After recognition of ICCs in the gut (15,16), several studies were performed to investigate the presence and distribution of pacemaker cells in the UUT. Some spindle-shaped c-kit-positive cells were detected in the UUT.…”