Rhythmic Cl? current and physiological roles of the intestinal c-kit-positive cells

Tokutomi, Naofumi; Maeda, Hirotaka; Tokutomi, Yoshiko; Sato, Daisuke; Sugita, Michiko; Nishikawa, Satomi; Nishikawa, Sin Ichi; Nakao, Junko; Imamura, Takayuki; Nishi, Katsuhide

doi:10.1007/bf00410188

Cited by 98 publications

(80 citation statements)

References 40 publications

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“…One report suggested that ICCs from the murine small intestine generated spontaneous Ca 2+ -activated Cl -currents (Tokutomi et al, 1995). This conclusion was based on pharmacological tests using a Cl -channel-blocking drug (4-acetoamido-4-isothiocyanat-ostilbene-2,2-disulphonic acid; SITS).…”

Section: Possible Mechanisms For the Pacemaker Activity In Interstitimentioning

confidence: 99%

The relationship of TRP channels to the pacemaker activity of interstitial cells of Cajal in the gastrointestinal tract

Kim

2006

J. Smooth Muscle Res.

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Interstitial cells of Cajal (ICCs) are a fundamental component of the pacemaker apparatus of the gastrointestinal (GI) tract. They have special properties that make them unique in their ability to generate and propagate slow waves in gastrointestinal smooth muscle. The pacemaker current that generates slow waves is initially due to a voltageindependent, Ca 2+ -inhibited, non-selective cationic conductance in ICC. The classical transient receptor potential (TRPC) channel 4 was suggested as a molecular candidate for the nonselective cation channel (NSCC) responsible for the pacemaker activity. We have shown that TRPC4-/-mice display normal slow waves and suggest that TRPC4 might be an essential component of the NSCC activated by muscarinic stimulation. Finally, we suggest that TRPM7 is the molecular candidate for the NSCC responsible for pacemaker activity in ICCs on the basis of electrophysiological, molecular biological, and immunohistochemical experiments.

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Section: Possible Mechanisms For the Pacemaker Activity In Interstitimentioning

confidence: 99%

The relationship of TRP channels to the pacemaker activity of interstitial cells of Cajal in the gastrointestinal tract

Kim

2006

J. Smooth Muscle Res.

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“…As colonic smooth muscle cell has only the high-threshold Ca-channels which are sensitive to organic Ca-antagonists [31], the pacemaker potential of the ICC is assumed to be produced by a sustained inward current carried through the low-threshold Ca-channels, analogous to pacemaker potentials in cardiac muscle. However, cultured ICC of the mouse intestine produce spontaneous membrane potential changes through opening Ca-activated Cl-channels [32]. The processes for the generation of spontaneous activity are suggested to be as follows: Ca 2ϩ released from internal stores activates Cl-channels to depolarize the membrane and, when the potential exceeds the threshold level, opens L-type Ca-channels to form a large depolarization.…”

Section: Spontaneous Activity Of Intestinal Smooth Musclesmentioning

confidence: 99%

Cellular Mechanisms of Myogenic Activity in Gastric Smooth Muscle.

Suzuki

2000

JJP

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Many types of smooth muscle contract spontaneously, with each contraction being accompanied by a slow rhythmic oscillation of the membrane potential (slow wave), a discharge of spike potentials or both [1]. The spontaneous generation of a single spike or bursts of spikes is detected in smooth muscles of the urinary bladder, the uterus (longitudinal muscle layer), the prostate, the isolated longitudinal muscle of the intestine or the portal vein. Slow waves are observed in smooth muscle of the stomach, the circular layer of the intestine and uterus of many species, the renal pelvis, the urethra and the ureter. In several of these muscles, spike potentials are followed. These include the renal pelvis, ureter, uterus (circular muscle), lymphatic vessels and the urethra [2]. As many enteric nerves generate bursts of activity, the transmitters released from these nerves can modulate the activity of smooth muscles [3], and there is a possibility that smooth muscle activity could result indirectly as a consequence of neuronal activity. However, this is rarely the cause of muscle activity since many smooth muscles remain active after neuronal activity has been that ICC may also be the pacemaker cells responsible for gastric activity. However, isolated circular smooth muscle tissues spontaneously generate regenerative potentials, suggesting that there are at least two sites for the initiation of spontaneous activity in the stomach. Regenerative potentials persist in the presence of Ca-antagonists and are inhibited by agents which disrupt intracellular Ca 2ϩ homeostasis. Depolarization of the membrane elicits regenerative potentials after a long delay and the potentials have long refractory periods. This suggests that an unidentified 2nd messenger may be formed during the delay between membrane depolarization and the initiation of a regenerative potential. In gastric muscles of mutant mice which do not express inositol trisphosphate (InsP 3 ) receptors, spike potentials but not slow waves are generated, suggesting the possible involvement of InsP 3 in the initiation of spontaneous activity.

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“…Furthermore, spontaneous inward currents are detected in isolated ICC, but not in gastrointestinal smooth muscle cells, when they are both maintained under cell culture conditions (Koh et al, 2002). The cellular mechanisms involved in this spontaneous activity in gastrointestinal tissues remain unclear, but are likely to involve cationic (Koh et al, 2001(Koh et al, , 2002, and/or Cl currents (Tokutomi et al, 1995;Huizinga et al, 2002). The spontaneous activity is not inhibited by several-type of organic Ca 2+ -antagonists such as verapamil (Golenhofen and Lammel, 1972), diltiazem (Ishikawa et al, 1985) and nifedipine (Dickens et al, 1999;Ishikawa et al, 2004;Liu et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Absence of peristalsis in the ileum of W/WV mutant mice that are selectively deficient in myenteric interstitial cells of Cajal

Nakagawa

Misawa

Nakajima

et al. 2005

J. Smooth Muscle Res.

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It is well known that the enteric nervous system plays a key role in the generation of gastrointestinal peristaltic movements. Recently, the networks of interstitial cells of Cajal (ICC) have been found to be essential in the generation of spontaneous gastrointestinal movements. However, the role of ICC in the mechanisms involved in the generation of peristaltic movements is still controversial. The aim of the present study was to reveal how pacemaker myenteric ICC (ICC-MY) and the enteric nervous system contribute to the mechanisms involved in the generation of intestinal peristalsis. We compared spontaneous peristaltic movements of the ileum in wild type (WT) mice with those in W/W V mutant mice which are selectively deficient in ICC-MY. Simultaneous recordings were made from both the circular and longitudinal muscle of a 4-cm long segment of ileum under hydrostatic pressure of 0-0.5 cm H2O. Mechanical activity and continuous videoimages of the ileum were compared between WT and W/W V mutant mice under control conditions, in the presence of N-nitro-L-arginine methyl ester (L-NAME) and after tetrodotoxin (TTX). In the WT mouse ileum, peristaltic waves to propagate from the oral to the anal end were frequently observed. The frequency of these peristaltic waves and their associated synchronous longitudinal and circular muscle contractions was increased by L-NAME. The peristaltic waves were abolished by TTX. In the W/W V mutant mouse ileum, no peristaltic waves to propagate from the oral to the anal end were observed in control and even after L-NAME, although the local spontaneously generated longitudinal and circular muscle contractions were enhanced by L-NAME. These local contractions were not abolished by TTX. The results presented here suggested that ICC-MY are essential for the generation of spontaneous intestinal peristaltic movements. It is conceivable that ICC-MY may determine the polarity of the excitation of the intestine such that longitudinal and circular muscle contractions propagate from the oral to the anal end of the intestinal segments, although the question of why ICC-MY are necessary for the neural pathways remains unresolved.

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Rhythmic Cl? current and physiological roles of the intestinal c-kit-positive cells

Cited by 98 publications

References 40 publications

The relationship of TRP channels to the pacemaker activity of interstitial cells of Cajal in the gastrointestinal tract

The relationship of TRP channels to the pacemaker activity of interstitial cells of Cajal in the gastrointestinal tract

Cellular Mechanisms of Myogenic Activity in Gastric Smooth Muscle.

Absence of peristalsis in the ileum of W/WV mutant mice that are selectively deficient in myenteric interstitial cells of Cajal

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