High-conductance chloride channels generate pacemaker currents in interstitial cells of Cajal

Huizinga, Jan D.; Zhu, Yingdong; Ye, Jing; Molleman, Areles

doi:10.1053/gast.2002.36549

Cited by 110 publications

(131 citation statements)

References 23 publications

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“…Also two additional papers have reported that both high conductance Cl -channels and inwardly rectifying Cl -channels participate in the pacemaker activity of ICCs (Huizinga et al, 2002;Zhu et al, 2005). A high-conductance chloride channel was spontaneously and rhythmically active at the same frequency as the rhythmic inward currents in ICC pacemaker activity and at the single channel level, while chloride channels were seen to be associated with the generation of the rhythmic changes in the membrane potential.…”

Section: Possible Mechanisms For the Pacemaker Activity In Interstitimentioning

confidence: 96%

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: 96%

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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“…Also in human jejunum, each ICC-MY generates spontaneous pacemaker activity that actively propagates through the ICC network, and the pacemaker activity was dependent on inositol-1,4,5-triphosphate receptor-operated stores and mitochondrial function [25] . Although some papers have identified the ion channels in ICCs [10,11,26,27] , there is little known about the ionic basis of its pacemaker activity. Recently, we used electrophysiological, molecular biological, and immunohistochemical techniques to establish the close relationship between NSCCs in ICCs and a mammalian TRP homologue, TRPM7 and found that TRPM7 is required for murine intestinal pacemaking [14] .…”

Section: Kim Bj Et Al Trpm7 and Interstitial Cells Of Cajalmentioning

confidence: 99%

Identifcation of TRPM7 channels in human intestinalinterstitial cells of Cajal

Kim¹,

Park²,

Kim³

et al. 2009

WJG

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AIM:To investigate the characteristics of slow electrical waves and the presence of transient receptor potential melastatin-type 7 (TRPM7) in the human gastrointestinal (GI) tract. METHODS:Conventional microelectrode techniques were used to record intracellular electrical responses from human GI smooth muscle tissue. Immunohistochemistry was used to identify TRPM7 channels in interstitial cells of Cajal (ICCs). RESULTS:The human GI tract generated slow electrical waves and had ICCs which functioned as pacemaker cells. Flufenamic acid, a nonselective cation channel blocker, and 2-APB (2-aminoethoxydiphenyl borate) and La 3+, TRPM7 channel blockers, inhibited the slow waves. Also, TRPM7 channels were expressed in ICCs in human tissue. CONCLUSION:These results suggest that the human GI tract generates slow waves and that TRPM7 channels expressed in the ICCs may be involved in the generation of the slow waves.

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“…S1P receptors also have a role in mobilization of intracellular Ca 2+ in various cell types (Bischoff et al, 2000;Spiegel and Merrill, 1996;Young and Nahorski, 2002). The pacemaking mechanisms of intestinal ICC are driven by activation of Ca 2+ -dependent pacemaker channels, such as TRP or Ca 2+ -activated Cl -channels, which are coupled with release of IP 3 -gated Ca 2+ from the endoplasmic reticulum (Huizinga et al, 2002;Kim et al, 2005;Nakayama et al, 2007;Ward et al, 2000). S1P stimulation of phosphoinositide hydrolysis and [Ca 2+ ] i increase in vascular smooth muscle, gastric smooth muscle, and HEK cells has been reported (Blom et al, 2005;Dragusin et al, 2006;Hemmings, 2006).…”

Section: Discussionmentioning

confidence: 99%

Effects of Sphingosine-1-Phosphate on Pacemaker Activity of Interstitial Cells of Cajal from Mouse Small Intestine

Han

Lee

Park

et al. 2013

Molecules and Cells

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Interstitial cells of Cajal (ICC) are the pacemaker cells that generate the rhythmic oscillation responsible for the production of slow waves in gastrointestinal smooth muscle. Spingolipids are known to present in digestive system and are responsible for multiple important physiological and pathological processes. In this study, we are interested in the action of sphingosine 1-phosphate (S1P) on ICC. S1P depolarized the membrane and increased tonic inward pacemaker currents. FTY720 phosphate (FTY720P, an S1P 1,3,4,5 agonist) and SEW 2871 (an S1P 1 agonist) had no effects on pacemaker activity. Suramin (an S1P 3 antagonist) did not block the S1P-induced action on pacemaker currents. However, JTE-013 (an S1P 2 antagonist) blocked the S1P-induced action. RT-PCR revealed the presence of the S1P 2 in ICC. Calphostin C (a protein kinase C inhibitor), NS-398 (a cyclooxygenase-2 inhibitor), PD 98059 (a p42/44 inhibitor), or SB 203580 (a p38 inhibitor) had no effects on S1P-induced action. However, c-jun NH 2 -terminal kinase (JNK) inhibitor II suppressed S1P-induced action. External Ca 2+ -free solution or thapsigargin (a Ca 2+ -ATPase inhibitor of endoplasmic reticulum) suppressed action of S1P on ICC. In recording of intracellular Ca 2+ ([Ca 2+ ] i ) concentration using fluo-4/AM S1P increased intensity of spontaneous [Ca 2+ ] i oscillations in ICC. These results suggest that S1P can modulate pacemaker activity of ICC through S1P 2 via regulation of external and internal Ca 2+ and mitogenactivated protein kinase activation.

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High-conductance chloride channels generate pacemaker currents in interstitial cells of Cajal

Cited by 110 publications

References 23 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

Identifcation of TRPM7 channels in human intestinalinterstitial cells of Cajal

Effects of Sphingosine-1-Phosphate on Pacemaker Activity of Interstitial Cells of Cajal from Mouse Small Intestine

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