Cellular and Molecular Basis for Electrical Rhythmicity in Gastrointestinal Muscles

Horowitz, Burton; Ward, Sean M.; Sanders, Kenton M.

doi:10.1146/annurev.physiol.61.1.19

Cited by 195 publications

(157 citation statements)

References 115 publications

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“…Molecular identification of ion channels important to smooth muscle function allows analysis of their biophysical, pharmacological, and regulatory properties in heterologous systems (20). In the present study, we have identified the molecular entity responsible for a component of stretch-activated K ϩ channels in gastrointestinal smooth muscle cells.…”

Section: Many Different Kmentioning

confidence: 84%

TREK-1 Regulation by Nitric Oxide and cGMP-dependent Protein Kinase

Koh

Monaghan

Sergeant

et al. 2001

Journal of Biological Chemistry

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126

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Potassium channels activated by membrane stretch may contribute to maintenance of relaxation of smooth muscle cells in visceral hollow organs. Previous work has identified K ؉ channels in murine colon that are activated by stretch and further regulated by NO-dependent mechanisms. We have screened murine gastrointestinal, vascular, bladder, and uterine smooth muscles for the expression of TREK and TRAAK mRNA. Although TREK-1 was expressed in many of these smooth muscles, TREK-2 was expressed only in murine antrum and pulmonary artery. TRAAK was not expressed in any smooth muscle cells tested. Whole cell currents from TREK-1 expressed in mammalian COS cells were activated by stretch, and single channel recordings showed that the stretch-dependent conductance was due to 90 pS channels. Sodium nitroprusside

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Section: Many Different Kmentioning

confidence: 84%

TREK-1 Regulation by Nitric Oxide and cGMP-dependent Protein Kinase

Koh

Monaghan

Sergeant

et al. 2001

Journal of Biological Chemistry

Self Cite

126

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“…Smooth muscle cells lack the ionic mechanisms necessary for slowwave regeneration (12,37). Thus, propagation of slow waves, a critical feature of normal gastric motility, requires intact IC-MY networks throughout the phasic regions of the stomach.…”

Section: Discussionmentioning

confidence: 99%

Remodeling of networks of interstitial cells of Cajal in a murine model of diabetic gastroparesis.

et al. 2000

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Patients with long-standing diabetes commonly suffer from gastric neuromuscular dysfunction (gastropathy) causing symptoms ranging from postprandial bloating to recurrent vomiting. Autonomic neuropathy is generally believed to be responsible for diabetic gastropathy and the underlying impairments in gastric emptying (gastroparesis) and receptive relaxation, but the specific mechanisms have not been elucidated. Recently, it has been recognized that interstitial cells of Cajal generate electrical pacemaker activity and mediate motor neurotransmission in the stomach. Loss or defects in interstitial cells could contribute to the development of diabetic gastroparesis. Gastric motility was characterized in spontaneously diabetic NOD/LtJ mice by measuring gastric emptying and by monitoring spontaneous and induced electrical activity in circular smooth muscle cells. Interstitial cells of Cajal were studied by Kit immunofluorescence and transmission electron microscopy. Diabetic mice developed delayed gastric emptying, impaired electrical pacemaking, and reduced motor neurotransmission. Interstitial cells of Cajal were greatly reduced in the distal stomach, and the normally close associations between these cells and enteric nerve terminals were infrequent. Our observations suggest that damage to interstitial cells of Cajal may play a key role in the pathogenesis of diabetic gastropathy.

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“…The gastric interstitial cells of Cajal (ICC) act as pacemaker cells and possess unique ionic conductances that trigger slow wave activity, whereas smooth muscle cells lack the basic mechanisms required to generate ECA. Instead, cells of the latter type respond to the depolarization and repolarization cycle imposed by the ICC network and regulate L-type Ca 2+ currents which are also responsible for the contractile behaviour of the stomach (Horowitz et al 1999). In both animals and humans, the antral region of the stomach has the capability of a pacemaker which generates and drives ECA slow waves along the gastric corpus in the direction of the pylorus (Horiguchi et al 2001).…”

Section: Introductionmentioning

confidence: 99%

Magnetogastrographic detection of gastric electrical response activity in humans

2006

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The detection and characterization of gastric electrical activity has important clinical applications, including the early diagnosis of gastric diseases in humans. In mammals, this phenomenon has two important features: an electrical control activity (ECA) that manifests itself as an electric slow wave (with a frequency of 3 cycles per minute in humans) and an electrical response activity (ERA) that is characterized by spiking potentials during the plateau phase of the ECA. Whereas the ECA has been recorded in humans both invasively and non-invasively (magnetogastrography-MGG), the ERA has never been detected non-invasively in humans before. In this paper, we report on our progress towards the non-invasive detection of ERA from the human stomach using a procedure that involves the application of principal component analysis to MGG recordings, which were acquired in our case from ten normal human patients using a Superconducting QUantum Interference Device (SQUID) magnetometer. Both pre-and post-prandial recordings were acquired for each patient and 20 min of recordings (10 min of pre-prandial and 10 min of post-prandial data) were analysed for each patient. The mean percentage of ECA slow waves that were found to exhibit spikes of suspected ERA origin was 41% and 61% for pre-and post-prandial recordings, respectively, implying a 47% ERA increase post-prandially (P < 0.0001 at a 95% confidence level). The detection of ERA in humans is highly encouraging and points to the possible use of non-invasive ERA recordings as a valuable tool for the study of human gastric disorders.

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Cellular and Molecular Basis for Electrical Rhythmicity in Gastrointestinal Muscles

Cited by 195 publications

References 115 publications

TREK-1 Regulation by Nitric Oxide and cGMP-dependent Protein Kinase

TREK-1 Regulation by Nitric Oxide and cGMP-dependent Protein Kinase

Remodeling of networks of interstitial cells of Cajal in a murine model of diabetic gastroparesis.

Magnetogastrographic detection of gastric electrical response activity in humans

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