Mechanosensitivity of STREX-lacking BKCa channels in the colonic smooth muscle of the mouse

2010 ◽  
Vol 299 (6) ◽  
pp. G1231-G1240 ◽  
Author(s):  
Wei Wang ◽  
Haixia Huang ◽  
Dongyan Hou ◽  
Ping Liu ◽  
Hua Wei ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Adult Mouse ◽  
Smooth Muscles ◽  
Cell Types ◽  
Potential Mechanism ◽  
Gi Tract ◽  
Bkca Channels ◽  
Α Subunit ◽  
Membrane Stretch ◽  
Mechanoelectric Transduction

Stretch sensitivity of Ca2+-activated large-conductance K+ channels (BKCa) has been observed in a variety of cell types and considered to be a potential mechanism in mechanoelectric transduction (MET). Mechanical stress is a major stimulator for the smooth muscle in the gastrointestinal (GI) tract. However, much about the role and mechanism of MET in GI smooth muscles remains unknown. The BKCa shows a functional diversity due to intensive Slo I alternative splicing and different α/β-subunit assembly in various cells. The stress-regulated exon (STREX) insert is suggested to be an indispensable domain for the mechanosensitivity of BKCa. The purpose of this study was to determine whether the BKCa in colonic myocytes of the adult mouse is sensitive to mechanical stimulation and whether the STREX insert is a crucial segment for the BKCa mechanosensitivity. The α- and β1-subunit mRNAs and the α-subunit protein of the BKCa channels were detected in the colonic muscularis. We found that the BKCa STREX-lacking variant was abundantly expressed in the smooth muscle, whereas the STREX variant was not detectable. We demonstrated that the STREX-lacking BKCa channels were also sensitive to membrane stretch. We suggest that in addition to the STREX domain, there are other additional structures in the channel responsible for mechanically coupling with the cell membrane.

Molecular diversity of KVα- and β-subunit expression in canine gastrointestinal smooth muscles

1999 ◽  
Vol 277 (1) ◽  
pp. G127-G136 ◽  
Author(s):  
Anne Epperson ◽  
Helena P. Bonner ◽  
Sean M. Ward ◽  
William J. Hatton ◽  
Karri K. Bradley ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Smooth Muscles ◽  
Muscle Cells ◽  
Pcr Analysis ◽  
Transcriptional Level ◽  
Gi Tract ◽  
Excitable Cells ◽  
Subunit Expression ◽  
Molecular Components

Voltage-activated K+(KV) channels play an important role in regulating the membrane potential in excitable cells. In gastrointestinal (GI) smooth muscles, these channels are particularly important in modulating spontaneous electrical activities. The purpose of this study was to identify the molecular components that may be responsible for the KV currents found in the canine GI tract. In this report, we have examined the qualitative expression of eighteen different KV channel genes in canine GI smooth muscle cells at the transcriptional level using RT-PCR analysis. Our results demonstrate the expression of KV1.4, KV1.5, KV1.6, KV2.2, and KV4.3 transcripts in all regions of the GI tract examined. Transcripts encoding KV1.2, KVβ1.1, and KVβ1.2 subunits were differentially expressed. KV1.1, KV1.3, KV2.1, KV3.1, KV3.2, KV3.4, KV4.1, KV4.2, and KVβ2.1 transcripts were not detected in any GI smooth muscle cells. We have also determined the protein expression for a subset of these KV channel subunits using specific antibodies by immunoblotting and immunohistochemistry. Immunoblotting and immunohistochemistry demonstrated that KV1.2, KV1.4, KV1.5, and KV2.2 are expressed at the protein level in GI tissues and smooth muscle cells. KV2.1 was not detected in any regions of the GI tract examined. These results suggest that the wide array of electrical activity found in different regions of the canine GI tract may be due in part to the differential expression of KV channel subunits.

scholarly journals Impact of naturally forming human α/β-tryptase heterotetramers in the pathogenesis of hereditary α-tryptasemia

2019 ◽  
Vol 216 (10) ◽  
pp. 2348-2361 ◽  
Author(s):  
Quang T. Le ◽  
Jonathan J. Lyons ◽  
Andrea N. Naranjo ◽  
Ana Olivera ◽  
Robert A. Lazarus ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Mast Cells ◽  
Clinical Features ◽  
Hormone Receptor ◽  
Cell Types ◽  
The Novel ◽  
Monogenic Disorder ◽  
Α Subunit ◽  
Gene Copies ◽  
Protease Activated Receptor 2

Both α-tryptase and β-tryptase are preferentially expressed by human mast cells, but the purpose of α-tryptase is enigmatic, because its tetramers lack protease activity, whereas β-tryptase tetramers are active proteases. The monogenic disorder called hereditary α-tryptasemia, due to increased α-tryptase gene copies and protein expression, presents with clinical features such as vibratory urticaria and dysautonomia. We show that heterotetramers composed of 2α- and 2β-tryptase protomers (α/β-tryptase) form naturally in individuals who express α-tryptase. α/β-Tryptase, but not homotetramer, activates protease-activated receptor-2 (PAR2), which is expressed on cell types such as smooth muscle, neurons, and endothelium. Also, only α/β-tryptase makes mast cells susceptible to vibration-triggered degranulation by cleaving the α subunit of the EGF-like module–containing mucin-like hormone receptor-like 2 (EMR2) mechanosensory receptor. Allosteric effects of α-tryptase protomers on neighboring β-tryptase protomers likely result in the novel substrate repertoire of α/β-tryptase tetramers that in turn cause some of the clinical features of hereditary α-tryptasemia and of other disorders involving mast cells.

A-type potassium currents in smooth muscle

2003 ◽  
Vol 284 (3) ◽  
pp. C583-C595 ◽  
Author(s):  
Gregory C. Amberg ◽  
Sang Don Koh ◽  
Yuji Imaizumi ◽  
Susumu Ohya ◽  
Kenton M. Sanders
Keyword(s):  
Smooth Muscle ◽  
Physiological Function ◽  
Smooth Muscles ◽  
Cell Types ◽  
Cardiac Cell ◽  
Biophysical Properties ◽  
Voltage Gated ◽  
Gastrointestinal Smooth Muscle ◽  
Molecular Identity ◽  
Rapid Activation

A-type currents are voltage-gated, calcium-independent potassium (Kv) currents that undergo rapid activation and inactivation. Commonly associated with neuronal and cardiac cell-types, A-type currents have also been identified and characterized in vascular, genitourinary, and gastrointestinal smooth muscle cells. This review examines the molecular identity, biophysical properties, pharmacology, regulation, and physiological function of smooth muscle A-type currents. In general, this review is intended to facilitate the comparison of A-type currents present in different smooth muscles by providing a comprehensive report of the literature to date. This approach should also aid in the identification of areas of research requiring further attention.

scholarly journals Hypoxic conditioning in blood vessels and smooth muscle tissues: effects on function, mechanisms, and unknowns

2018 ◽  
Vol 315 (4) ◽  
pp. H756-H770 ◽  
Author(s):  
Asmaa M. Almohanna ◽  
Susan Wray
Keyword(s):  
Smooth Muscle ◽  
Blood Vessels ◽  
Contractile Activity ◽  
Smooth Muscles ◽  
Cell Types ◽  
Hypoxic Preconditioning ◽  
Visceral Organs ◽  
Muscle Tissues ◽  
Force Increase ◽  
Liver And Kidney

Hypoxic preconditioning, the protective effect of brief, intermittent hypoxic or ischemic episodes on subsequent more severe hypoxic episodes, has been known for 30 yr from studies on cardiac muscle. The concept of hypoxic preconditioning has expanded; excitingly, organs beyond the heart, including the brain, liver, and kidney, also benefit. Preconditioning of vascular and visceral smooth muscles has received less attention despite their obvious importance to health. In addition, there has been no attempt to synthesize the literature in this field. Therefore, in addition to overviewing the current understanding of hypoxic conditioning, in the present review, we consider the role of blood vessels in conditioning and explore evidence for conditioning in other smooth muscles. Where possible, we have distinguished effects on myocytes from other cell types in the visceral organs. We found evidence of a pivotal role for blood vessels in conditioning and for conditioning in other smooth muscle, including the bladder, vascular myocytes, and gastrointestinal tract, and a novel response in the uterus of a hypoxic-induced force increase, which helps maintain contractions during labor. To date, however, there are insufficient data to provide a comprehensive or unifying mechanism for smooth muscles or visceral organs and the effects of conditioning on their function. This also means that no firm conclusions can be drawn as to how differences between smooth muscles in metabolic and contractile activity may contribute to conditioning. Therefore, we have suggested what may be general mechanisms of conditioning occurring in all smooth muscles and tabulated tissue-specific mechanistic findings and suggested ideas for further progress.

Nitric oxide as a mediator of nonadrenergic noncholinergic neurotransmission

1992 ◽  
Vol 262 (3) ◽  
pp. G379-G392 ◽  
Author(s):  
K. M. Sanders ◽  
S. M. Ward
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Nerve Stimulation ◽  
Smooth Muscles ◽  
Extracellular Fluid ◽  
Electrical Field Stimulation ◽  
Enteric Neurons ◽  
Field Stimulation ◽  
Gi Tract

Part of the regulation of gastrointestinal (GI) smooth muscles is provided by nonadrenergic noncholinergic (NANC) nerves. Stimulation of these nerves, either by field stimulation or via neural reflex pathways, elicits hyperpolarization of postjunctional smooth muscle membranes referred to as inhibitory junction potentials and relaxation. The transmitter(s) that mediate NANC inhibitory neural transmission have been a controversial topic for nearly 30 years. Recent evidence suggests that nitric oxide (NO) may serve as a NANC inhibitory transmitter in the GI tract. This hypothesis is supported by the following. 1) Immunohistochemical studies have shown that the enzyme necessary for NO synthesis is expressed in enteric neurons. In vitro studies of muscles from nearly all levels of GI tract have also shown that arginine analogues, which inhibit NO synthesis, reduce inhibitory effects of NANC neurotransmission. Effects of arginine analogues can be restored by addition of excess L-arginine, the substrate for NO synthesis. These data suggest that NO can be synthesized by enteric nerves. 2) Bioassays have demonstrated nerve-evoked release of a substance that has been identified as NO during NANC nerve stimulation. Oxyhemoglobin, known to bind to and sequester NO, also blocks NANC responses. These data suggest that NO is released into extracellular fluid during nerve stimulation. 3) Addition of NO causes rapid hyperpolarization of GI smooth muscle cells and relaxes muscles strips. These effects are similar to NANC nerve responses. NO and electrical field stimulation also increase tissue guanosine 3',5'-cyclic monophosphate, which may be the second messenger involved in NANC responses. 4) Removal of NO is easily accomplished by its rapid spontaneous breakdown in physiological solutions. 5) The pharmacology of NO and the NANC neurotransmitter in many preparations is similar, e.g., oxyhemoglobin blocks responses to NANC nerve stimulation and to exogenous NO. In summary, it would appear that many of the criteria necessary for NO to be considered a neurotransmitter have been satisfied.

scholarly journals Changes in the Contractile Activity and Reactivity to 5-HT of Smooth Muscles of Rats Following Total Body Irradiation with Accelerated Electrons

Folia Medica ◽  
2019 ◽  
Vol 61 (3) ◽  
pp. 411-418 ◽  
Author(s):  
Xenodochidis A. Charilaos ◽  
Raina G. Ardasheva ◽  
Veselin G. Popov ◽  
Natalia A. Prissadova ◽  
Valentin I. Turiyski ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Total Body Irradiation ◽  
Serotonin Receptors ◽  
Contractile Activity ◽  
Smooth Muscles ◽  
Control Group ◽  
Gi Tract ◽  
Circular Smooth Muscle ◽  
Muscle Tissues ◽  
Total Body

Background: Besides its “classical” neurotransmitter function in the central and peripheral nervous systems, serotonin, or 5-hydroxytryptamine (5-HT) is also a local hormone in a number of tissues, including those of the GI tract. Radiation is known to be able to disrupt certain functions of the tract, modulated by 5-HT-signaling pathways, or the serotonin receptors themselves. Aim: The present investigation focused on clarifying the nature and extent of influence of an accelerated electron beam with energy of 9 MeV on the serotonergic mediation of healthy smooth muscle gastric tissue of rats following total body irradiation of the animals. Materials and methods: The study involved a control group and two experimental groups of animals exposed to 1 and 5 Gy, respectively, using Siemens Primus S/N 3561. Circular smooth muscle tissues were isolated from rats 1 hour and 18 hours after they were exposed to 1 and 5 Gy and also 5 days after irradiation from the rats that received a dose of 5 Gy in order to investigate the action of exogenous serotonin at increasing concentrations from 10-8 to 10-4 mol/l. The contractile reactivity of each group SM preparations was registered isometrically. Results: Electron beams with energy of 9 MeV did not damage the contractile apparatus of gastric SM of rats and had a stimulating effect on contractility resulting from rapidly developing processes (1 hour) or later occurring once (5 days). Conclusions: Difference was observed in the importance of the factors of received dose, lapse of time from irradiation to investigation of SM tissues, and exogenous 5-HT concentration for the changes in SM reactivity in serotonin-induced tonic and phasic responses.

scholarly journals Influence of layer separation on the determination of stomach smooth muscle properties

2021 ◽  
Author(s):  
Mischa Borsdorf ◽  
Markus Böl ◽  
Tobias Siebert
Keyword(s):  
Smooth Muscle ◽  
Muscle Fibers ◽  
Smooth Muscles ◽  
Muscle Layer ◽  
Uniaxial Tensile ◽  
Muscle Properties ◽  
Layer Separation ◽  
Isotonic Contractions ◽  
Longitudinal Layer

AbstractUniaxial tensile experiments are a standard method to determine the contractile properties of smooth muscles. Smooth muscle strips from organs of the urogenital and gastrointestinal tract contain multiple muscle layers with different muscle fiber orientations, which are frequently not separated for the experiments. During strip activation, these muscle fibers contract in deviant orientations from the force-measuring axis, affecting the biomechanical characteristics of the tissue strips. This study aimed to investigate the influence of muscle layer separation on the determination of smooth muscle properties. Smooth muscle strips, consisting of longitudinal and circumferential muscle layers (whole-muscle strips [WMS]), and smooth muscle strips, consisting of only the circumferential muscle layer (separated layer strips [SLS]), have been prepared from the fundus of the porcine stomach. Strips were mounted with muscle fibers of the circumferential layer inline with the force-measuring axis of the uniaxial testing setup. The force–length (FLR) and force–velocity relationships (FVR) were determined through a series of isometric and isotonic contractions, respectively. Muscle layer separation revealed no changes in the FLR. However, the SLS exhibited a higher maximal shortening velocity and a lower curvature factor than WMS. During WMS activation, the transversally oriented muscle fibers of the longitudinal layer shortened, resulting in a narrowing of this layer. Expecting volume constancy of muscle tissue, this narrowing leads to a lengthening of the longitudinal layer, which counteracted the shortening of the circumferential layer during isotonic contractions. Consequently, the shortening velocities of the WMS were decreased significantly. This effect was stronger at high shortening velocities.

scholarly journals Remodeling of Arterial Tone Regulation in Postnatal Development: Focus on Smooth Muscle Cell Potassium Channels

2021 ◽  
Vol 22 (11) ◽  
pp. 5413
Author(s):  
Anastasia A. Shvetsova ◽  
Dina K. Gaynullina ◽  
Olga S. Tarasova ◽  
Rudolf Schubert
Keyword(s):  
Smooth Muscle ◽  
Potassium Channels ◽  
Potassium Channel ◽  
Postnatal Development ◽  
Sympathetic Innervation ◽  
Treatment Strategies ◽  
Muscle Membrane ◽  
Postnatal Life ◽  
Vascular Control ◽  
Bkca Channels

Maturation of the cardiovascular system is associated with crucial structural and functional remodeling. Thickening of the arterial wall, maturation of the sympathetic innervation, and switching of the mechanisms of arterial contraction from calcium-independent to calcium-dependent occur during postnatal development. All these processes promote an almost doubling of blood pressure from the moment of birth to reaching adulthood. This review focuses on the developmental alterations of potassium channels functioning as key smooth muscle membrane potential determinants and, consequently, vascular tone regulators. We present evidence that the pattern of potassium channel contribution to vascular control changes from Kir2, Kv1, Kv7 and TASK-1 channels to BKCa channels with maturation. The differences in the contribution of potassium channels to vasomotor tone at different stages of postnatal life should be considered in treatment strategies of cardiovascular diseases associated with potassium channel malfunction.

scholarly journals Do GISTs Occur in Rats and Mice? Immunohistochemical Characterization of Gastrointestinal Tumors Diagnosed as Smooth Muscle Tumors in The National Toxicology Program

2019 ◽  
Vol 47 (5) ◽  
pp. 577-584
Author(s):  
Kyathanahalli S. Janardhan ◽  
Priyanka Venkannagari ◽  
Heather Jensen ◽  
Mark J. Hoenerhoff ◽  
Ronald A. Herbert ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Cell Morphology ◽  
Spindle Cell ◽  
Smooth Muscle Actin ◽  
Gi Tract ◽  
Toxicological Studies ◽  
Smooth Muscle Tumors ◽  
Hematoxylin And Eosin ◽  
Cells Of Cajal ◽  
Rats And Mice

The majority of the tumors in the gastrointestinal (GI) tract of rats and mice, with spindle cell morphology, are diagnosed as smooth muscle tumors (SMTs). Similarly, several decades ago human GI tumors with spindle cell morphology were also diagnosed as SMTs. However, later investigations identified most of these tumors in humans as gastrointestinal stromal tumors (GISTs). The GISTs are considered to arise from the interstitial cells of Cajal located throughout the GI tract. Positive immunohistochemical staining with CKIT antibody is a well-accepted diagnostic marker for GISTs in humans. Since there is a considerable overlap between the histomorphology of SMTs and GISTs, it is not possible to distinguish them on hematoxylin and eosin stained sections. As a result, GISTs are not routinely diagnosed in toxicological studies. The current study was designed to evaluate the tumors diagnosed as leiomyoma or leiomyosarcoma in the National Toxicology Program’s 2-year bioassays using CKIT, smooth muscle actin, and desmin immunohistochemistry. The results demonstrate that most of the mouse SMTs diagnosed as leiomyoma or leiomyosarcoma are likely GISTs, whereas in rats the tumors are likely SMTs and not GISTs.

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