A5047237994- Ion channel regulation and function
- Gastrointestinal motility and disorders
- Ion Channels and Receptors
- Ion Transport and Channel Regulation
- Cardiac electrophysiology and arrhythmias
- Erythrocyte Function and Pathophysiology
- Neuroscience and Neuropharmacology Research
- Helicobacter pylori-related gastroenterology studies
- Nicotinic Acetylcholine Receptors Study
- Digestive system and related health
- Chemical and Physical Studies
- Congenital gastrointestinal and neural anomalies
- Lipid Membrane Structure and Behavior
- Protein Kinase Regulation and GTPase Signaling
- Gastrointestinal disorders and treatments
- Hydrogen's biological and therapeutic effects
- Neuroscience of respiration and sleep
- Biochemical Analysis and Sensing Techniques
- Plant and Biological Electrophysiology Studies
- Caveolin-1 and cellular processes
- Infant Health and Development
- Diabetes and associated disorders
- Phosphodiesterase function and regulation
- Melanoma and MAPK Pathways
- Calcium signaling and nucleotide metabolism
Mayo Clinic
2011-2024
WinnMed
2002-2024
Mayo Clinic in Florida
2010-2022
Mayo Clinic in Arizona
2008-2021
University of Wisconsin–Madison
2012
University of Minnesota Rochester
2012
Chung-Ang University
2006
University of Minnesota
2000
Enterochromaffin (EC) cells constitute the largest population of intestinal epithelial enteroendocrine (EE) cells. EC are proposed to be specialized mechanosensory that release serotonin in response forces, and thereby regulate fluid secretion. However, it is unknown whether EE directly mechanosensitive, if so, what molecular mechanism their mechanosensitivity is. Consequently, role gastrointestinal mechanobiology unclear. Piezo2 mechanosensitive ion channels important for some...
The voltage-sensitive sodium channel Na(v)1.5 (encoded by SCN5A) is expressed in electromechanical organs and mechanosensitive. This study aimed to determine the mechanosensitive transitions of at molecular level. was HEK 293 cells mechanosensitivity studied cell-attached patches. Patch pressure up -50 mmHg produced increases current large hyperpolarizing shifts voltage dependence with graded half-activation half-inactivation voltages (V(1/2)) ∼0.7 mV mmHg(-1). Voltage affected kinetics a...
Interstitial cells of Cajal (ICC) generate the electrical slow wave required for normal gastrointestinal motility. The ionic conductances expressed in human intestinal ICC are unknown. aim this study was to determine expression a Na + current and effects on wave. Visually identified, freshly dissociated, single were verified by presence c- kit mRNA using single-cell RT-PCR. Standard whole cell currents recorded from patch-clamped held at -100 mV between pulse protocols. A identified ICC....
The SCN5A-encoded Na(v)1.5 Na(+) channel is expressed in interstitial cells of Cajal and smooth muscle the circular layer human intestine. Patients with mutations SCN5A are more likely to report gastrointestinal symptoms, especially abdominal pain. Twin family studies irritable bowel syndrome (IBS) suggest a genetic basis for IBS, but no genes have been identified date. Therefore, our aims were evaluate as candidate gene involved pathogenesis IBS determine physiological consequences...
Diabetes affects many organs including the stomach. Altered number and function of interstitial cells Cajal (ICC), gastrointestinal pacemaker cells, underlie a motility disorders, diabetic gastroparesis. In muscle layers, ICC selectively express Ano1, thought to classical Ca2+-activated Cl− currents. Mice homozygous for Ano1 knock-out exhibit abnormal motility. Several transcripts are generated by alternative splicing four exons. Here, we report expression levels encoded gene in gastric...
Smooth muscle exhibits mechanosensitivity independent of neural input, suggesting that mechanosensitive pathways reside within smooth cells. The native L-type calcium current recorded from human intestinal is modulated by stretch. To define mechanisms involved in the regulation entry, we cloned α 1C channel subunit (Ca V 1.2) and expressed a heterologous system. This retained when alone or coexpressed with β 2 HEK-293 Chinese hamster ovary heterologously cardiac splice form also demonstrated...
ABSTRACT We have isolated one member of the frizzled family wnt receptors from Xenopus (Xfz7) to study role cell-cell communication in establishment vertebrate axis. demonstrate that this maternally encoded protein specifically synergizes with proteins ectopic axis induction. Embryos derived oocytes depleted maternal Xfz7 RNA by antisense oligonucleotide injection are deficient dorsoanterior structures. Xfz7-depleted embryos dorsal but not ventral mesoderm due reduced expression target genes...
<i>SCN5A</i> encodes the α subunit of cardiac muscle and intestinal smooth mechanosensitive Na<sup>+</sup> channel. Mechanosensitivity in intestine requires an intact cytoskeleton. We report, using laser capture microdissection, single cell PCR, immunohistochemistry, that syntrophins, scaffolding proteins, were expressed human cells. The distribution syntrophin γ2 was similar to SCN5A. Yeast two-hybrid glutathione <i>S</i>-transferase pull-down experiments show SCN5A co-express PDZ domain...
Background— Na V 1.5 is a mechanosensitive voltage-gated sodium-selective ion channel responsible for the depolarizing current and maintenance of action potential plateau in heart. Ranolazine antagonist with antianginal antiarrhythmic properties. Methods Results— Mechanosensitivity was tested voltage-clamped whole cells cell-attached patches by bath flow patch pressure, respectively. In cells, increased peak inward both murine ventricular cardiac myocytes (24±8%) human embryonic kidney 293...
The SCN5A-encoded voltage-gated mechanosensitive Na + channel V 1.5 is expressed in human gastrointestinal smooth muscle cells and interstitial of Cajal. contributes to electrical slow waves mechanical sensitivity. In predominantly Caucasian irritable bowel syndrome (IBS) patient cohorts, 2–3% patients have SCN5A missense mutations that alter function may contribute IBS pathophysiology. this study we examined a racially ethnically diverse cohort for mutations, compared them with IBS-negative...
Objective Haemorrhoidal disease (HEM) affects a large and silently suffering fraction of the population but its aetiology, including suspected genetic predisposition, is poorly understood. We report first genome-wide association study (GWAS) meta-analysis to identify risk factors for HEM date. Design conducted GWAS 218 920 patients with 725 213 controls European ancestry. Using summary statistics, we performed multiple correlation analyses between other traits as well calculated polygenic...
In the gastrointestinal (GI) epithelium, enterochromaffin (EC) cells are enteroendocrine responsible for producing >90% of body's serotonin (5-hydroxytryptamine, 5-HT). However, molecular mechanisms EC cell function poorly understood. Here, we found that in mouse primary cultures fired spontaneous bursts action potentials. We examined repertoire voltage-gated sodium channels (NaV) fluorescence-sorted and Scn3a was highly expressed. Scn3a-encoded NaV1.3 specifically densely expressed at basal...
A Na + current is present in human jejunal circular smooth muscle cells. The aim of the study was to determine role cytoskeleton regulation current. Whole cell currents were recorded by using standard patch-clamp techniques with Cs pipette block K currents. Cytochalasin D and gelsolin used disrupt actin phalloidin stabilize it. Colchicine disassemble microtubule (and intermediate filaments) paclitaxel Acrylamide filament cytoskeleton. Perfusion recording chamber at 10 ml/min increased peak...
Abstract Tetrodotoxin‐resistant Na + currents are expressed in a variety of muscle cells including human jejunal circular smooth (HJCSM) cells. The aim this study was to determine the molecular identity pore‐forming α‐subunit HJCSM channel. Degenerate primers identified cDNA fragment 1.5 kb with 99% nucleotide homology cardiac SCN5A. clone also amplified from single by reverse transcriptase–polymerase chain reaction (RT–PCR). Northern blot analysis showed expression full‐length Laser capture...
Carbon monoxide (CO) is increasingly recognized as a physiological messenger. CO produced in the gastrointestinal tract with diverse functions, including regulation of motility, interacting nitric oxide (NO) to mediate neurotransmission. The aim this study was determine effect on human intestinal L-type Ca(2+) channel expressed HEK cells and native using patch-clamp technique. Extracellular solution contained 10 mM Ba(2+) charge carrier. Maximal peak current (I(Ba)) significantly increased...
Interstitial cells of Cajal (ICC) generate the electrical slow wave. The ionic conductances that contribute to wave appear vary among species. In humans, a tetrodotoxin-resistant Na + current (Na V 1.5) encoded by SCN5A contributes rising phase wave, whereas T-type Ca 2+ currents have been reported from cultured mouse intestine ICC and also canine colonic ICC. Mibefradil has higher affinity for over L-type channels, drug used in gastrointestinal tract identify currents. However, selectivity...
Hydrogen sulfide (H(2)S) is produced endogenously by L-cysteine metabolism. H(2)S modulates several ion channels with an unclear mechanism of action. A possible through reduction-oxidation reactions attributable to the redox potential sulfur moiety. The aims this study were determine effects donor NaHS on Na(V)1.5, a voltage-dependent sodium channel expressed in gastrointestinal tract human jejunum smooth muscle cells and interstitial Cajal, elucidate whether acts Na(V)1.5 reactions. Whole...
Human jejunum smooth muscle cells (SMCs) and interstitial of Cajal (ICCs) express the SCN5A-encoded voltage-gated, mechanosensitive sodium channel NaV1.5. NaV1.5 contributes to small bowel excitability, inhibitor ranolazine produces constipation by an unknown mechanism. We aimed determine presence molecular identity Na(+) current in human colon examine effects on current, mechanosensitivity, contractility. Inward currents were recorded whole cell voltage clamp from freshly dissociated SMCs...
This study was designed to evaluate the roles of microRNAs (miRNAs) in slow transit constipation (STC).All human tissue samples were from muscularis externa colon. Expression 372 miRNAs examined a discovery cohort four patients with STC versus three age/sex-matched controls by quantitative PCR array. Upregulated reverse transcription qPCR (RT-qPCR) validation seven and controls. The effect highly differentially expressed miRNA on custom smooth muscle cell line vitro RT-qPCR,...