Effect of nitric oxide on calcium-activated potassium channels in colonic smooth muscle of rabbits

1998 ◽  
Vol 274 (5) ◽  
pp. G848-G856 ◽  
Author(s):  
Gang Lu ◽  
Bruno Mazet ◽  
Michael G. Sarr ◽  
Joseph H. Szurszewski
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Nerve Fibers ◽  
Nadph Diaphorase ◽  
Whole Cell ◽  
Circular Smooth Muscle ◽  
Rabbit Colon ◽  
Inside Out

Nitric oxide (NO) hyperpolarizes intestinal smooth muscle cells. This study was designed to determine the mechanism whereby NO activates KCa channels of circular smooth muscle of the rabbit colon. Transmural biopsies of the rabbit colon were stained for NADPH-diaphorase. Freshly dispersed circular smooth muscle cells were studied in the whole cell configuration, as well as in on-cell and excised inside-out patch recording configurations, while KCa current and the activity of KCa channels, respectively, were monitored. NADPH-diaphorase-positive nerve fibers were found in both muscle layers. NO (1%) increased whole cell net outward current by 79% and hyperpolarized resting membrane voltage from −59 to −73 mV ( n = 8 cells, P < 0.01). In the on-cell patch recording configuration, NO (0.5% or 1%) in the bath increased NP o of KCa channels; charybdotoxin (125 nM) in the pipette solution blocked this effect. In the excised inside-out patch recording configuration, NO (1%) had no effect on NP o of KCa channels. In the on-cell patch recording configuration, methylene blue (1 μM) or cystamine (5 mM) in the bath solution decreased the effect of NO (1%) on NP o of KCa channels. NP o was increased by 8-bromo-cGMP (8-BrcGMP; 1 mM), a cGMP analog, and zaprinast (100 μM), an inhibitor of cGMP phosphodiesterase. These data suggest that NO increased whole cell outward K+current by activating KCa channels through a cGMP pathway.

Nitric oxide modulates a calcium-activated potassium current in muscle cells from opossum esophagus

1995 ◽  
Vol 269 (4) ◽  
pp. G606-G612 ◽  
Author(s):  
J. A. Murray ◽  
E. F. Shibata ◽  
T. L. Buresh ◽  
H. Picken ◽  
B. W. O'Meara ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Protein Kinase ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Protein Kinase G ◽  
Patch Clamp Technique ◽  
Whole Cell ◽  
Circular Smooth Muscle ◽  
K Current

Nitric oxide mediates nerve-induced hyperpolarization of circular smooth muscle of the esophagus. Two mechanisms are proposed to explain this hyperpolarization: an increase in K+ current or a decrease in Cl- current. These studies test the hypothesis that nitric oxide increases a K+ current in esophageal smooth muscle. Three outward K+ currents are present in circular smooth muscle cells from the opossum esophagus. One current is a Ca(2+)-activated K+ current (IKCa2+). This current is inhibited by charybdotoxin. Whole cell currents were recorded from isolated opossum esophageal smooth muscle cells using the whole cell patch-clamp technique. These studies showed that IKCa2+ is activated at potentials more positive than -30 mV. Bath application of S-nitroso-L-cysteine increased IKCa2+ by 50% above control levels throughout the entire activation range of potentials. The enhanced current was reversible on washout. Either charybdotoxin, an inhibitor of IKCa2+, or (R)-p-8-(4-chloropenylthio)-guanosine 3',5'-cyclic monophosphorothioate, an inhibitor of protein kinase G, antagonized the increase in outward current induced by S-nitroso-L-cysteine. These data suggest that nitric oxide activates IKCa2+ via the guanosine 3',5'-cyclic monophosphate-protein kinase G signal transduction pathway.

scholarly journals Modulatory role of nitric oxide in cardiac performance

2014 ◽  
Vol 67 (9-10) ◽  
pp. 345-352 ◽  
Author(s):  
Sonja Smiljic ◽  
Vojkan Nestorovic ◽  
Sladjana Savic
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Free Radical ◽  
Nitric Oxide Synthase ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Nerve Fibers ◽  
Cardiac Insufficiency ◽  
Cellular Respiration ◽  
Oxide Synthase

Nitric oxide is produced by almost all cardiac cells, endothelial cells, cardiomyocytes and nerve fibers. It is synthesized by an enzyme, a nitric oxide synthase, which occurs in endothelial, neural and inducible form. The distribution of nitric oxide synthase in the heart is characterized by a pronounced non-uniformity. Nitric oxide exerts its effects in physiological and pathophysiological conditions. The physiological effects of low concentrations of nitric oxide, which is released in the normal conditions under the influence of constituent enzymes, occur via cyclic guanosine monophosphate. The synthesized nitric oxide exhibits its effect in the cells where it is produced, in an autocrine manner, or by diffusing into the neighboring cells, in a paracrine manner. Nitric oxide acts by regulating the coronary vessel tonus, affecting the contractility of cardiomyocytes, generating an inotropic effect in a dose-dependent manner and controlling the cellular respiration. Other effects of nitric oxide in the cardiovascular system include the hyperpolarization of the smooth muscle cells in blood vessels, the inhibition of the monocyte adhesion, the inhibition of platelet migration, adhesion and aggregation and the proliferation of smooth muscle cells and fibroblasts. The anti-atherosclerotic effects of nitric oxide are based on these effects. Nitric oxide is a weak free radical in gaseous state, and the cytotoxic and/or the cytoprotective effects of the higher concentrations of nitric oxide are related to the chemical structure of nitric oxide as a free radical. The excessive production of nitric oxide by the activation of inducible nitric oxide synthase can lead to major irregularities in the function of cardiomyocytes and cardiac insufficiency. Understanding the nitric oxide molecular mechanisms of signaling pathways in the heart can provide a new strategic approach to prevention and treatment of cardiovascular diseases.

Whole cell current and membrane potential regulation by a human smooth muscle mechanosensitive calcium channel

2000 ◽  
Vol 279 (6) ◽  
pp. G1155-G1161 ◽  
Author(s):  
Adrian N. Holm ◽  
Adam Rich ◽  
Michael G. Sarr ◽  
Gianrico Farrugia
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Smooth Muscle Cells ◽  
Outward Current ◽  
Muscle Cells ◽  
Membrane Hyperpolarization ◽  
Whole Cell ◽  
Circular Smooth Muscle ◽  
Channel Current ◽  
Cell Current

Mechanotransduction is required for a wide variety of biological functions. The aim of this study was to determine the effect of activation of a mechanosensitive Ca2+ channel, present in human jejunal circular smooth muscle cells, on whole cell currents and on membrane potential. Currents were recorded using patch-clamp techniques, and perfusion of the bath (10 ml/min, 30 s) was used to mechanoactivate the L-type Ca2+ channel. Perfusion resulted in activation of L-type Ca2+ channels and an increase in outward current from 664 ± 57 to 773 ± 72 pA at +60 mV. Membrane potential hyperpolarized from −42 ± 4 to −50 ± 5 mV. In the presence of nifedipine (10 μM), there was no increase in outward current or change in membrane potential with perfusion. In the presence of charybdotoxin or iberiotoxin, perfusion of the bath did not increase outward current or change membrane potential. A model is proposed in which mechanoactivation of an L-type Ca2+ channel current in human jejunal circular smooth muscle cells results in increased Ca2+ entry and cell contraction. Ca2+ entry activates large-conductance Ca2+-activated K+channels, resulting in membrane hyperpolarization and relaxation.

Interstitial cells in deep muscular plexus of canine small intestine may be specialized smooth muscle cells

1993 ◽  
Vol 265 (4) ◽  
pp. G638-G645 ◽  
Author(s):  
S. Torihashi ◽  
S. Kobayashi ◽  
W. T. Gerthoffer ◽  
K. M. Sanders
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Smooth Muscle Actin ◽  
Circular Muscle ◽  
Muscle Cells ◽  
Interstitial Cells ◽  
Nerve Fibers ◽  
Muscle Actin ◽  
Circular Smooth Muscle ◽  
Thick Filaments

The fine structures and properties of cells between the inner and outer circular muscle layers in the canine small intestine were studied by transmission electron microscopy (TEM), immunocytochemistry, and scanning electron microscopy (SEM). A nerve plexus (deep muscular plexus) supported by enteroglial cells, fibroblasts around blood vessels, macrophages, and thin and branched cells previously identified as interstitial cells of Cajal was observed. The interstitial cells of the deep muscular plexus (IC-DMP) were rich in mitochondria, dense bodies, and caveolae, and they were closely associated with nerve fibers. The IC-DMP had incomplete basal laminae. These cells also had numerous interconnecting gap junctions, and they also formed gap junctions with the surrounding smooth muscle cells of the outer circular muscle layer. IC-DMP were rich in myofilaments, which were primarily actin thin filaments, but myosin thick filaments, identified with anti-myosin light-chain antibodies, were also apparent. IC-DMP and circular smooth muscle cells both expressed immunoreactivity to anti-smooth muscle actin antisera, but these two types of cells differed in their intermediate filament proteins: IC-DMP featured vimentin immunopositive filaments, and circular smooth muscle cells featured desmin immunoreactivity. SEM showed that IC-DMP had thin and flat cell bodies with numerous branching processes. These cells came into close contact with nerve fibers and circular smooth muscle cells. The findings that IC-DMP cells contained myosin thick filaments and were immunopositive for anti-smooth muscle actin suggest that they may be more properly categorized as a type of smooth muscle cell.

Ca2+-dependent Cl− channels in mouse and rabbit aortic smooth muscle cells: regulation by intracellular Ca2+ and NO

1999 ◽  
Vol 277 (5) ◽  
pp. H1732-H1744 ◽  
Author(s):  
Yoji Hirakawa ◽  
Marion Gericke ◽  
Richard A. Cohen ◽  
Victoria M. Bolotina
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Single Channels ◽  
Whole Cell ◽  
Aortic Smooth Muscle Cells ◽  
Aortic Smooth Muscle ◽  
Intracellular Ca ◽  
Single Formula ◽  
Inside Out

Ca2+-dependent Cl− ([Formula: see text]) channels and their regulation by intracellular Ca2+concentration ([Ca2+]i) and nitric oxide (NO) were characterized in mouse and rabbit aortic smooth muscle cells (SMC) using patch clamp and fura 2 imaging. Single channels (1.8 pS) and whole cell[Formula: see text] currents were activated by caffeine-induced Ca2+ release. Single [Formula: see text] channels were also activated by ≥200 nM Ca2+ in inside-out membrane patches and remained active for >5 min in ≤1 μM Ca2+ but showed rapid rundown in 2 mM Ca2+. Authentic NO or S-nitroso- N-acetylpenicillamine (SNAP) did not affect their activation or rundown in inside-out patches. In the whole cell, SNAP (100 μM) and 8-(4-chlorophenylthio)-guanosine 3′,5′-cyclic monophosphate (50 μM) did not affect [Formula: see text]current, but at a higher concentration SNAP (1 mM) induced a sustained [Ca2+]irise, accompanied by a dramatic decrease in caffeine-induced Ca2+ release and[Formula: see text] current. These results indicate that 1) mouse and rabbit aortic SMC possess 1.8-pS [Formula: see text]channels that are activated by Ca2+ release from the stores, 2) both activation and rundown of single [Formula: see text] channels depend on [Ca2+]i, and 3) NO does not affect[Formula: see text] channels directly or via cGMP but can inhibit their activation indirectly by decreasing Ca2+ release from the stores.

Distribution of heme oxygenase and effects of exogenous carbon monoxide in canine jejunum

1998 ◽  
Vol 274 (2) ◽  
pp. G350-G358 ◽  
Author(s):  
G. Farrugia ◽  
S. M. Miller ◽  
A. Rich ◽  
X. Liu ◽  
M. D. Maines ◽  
...  
Keyword(s):  
Carbon Monoxide ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Heme Oxygenase ◽  
Neuronal Cell ◽  
Muscle Cells ◽  
Nerve Fibers ◽  
Whole Cell ◽  
Cell Current ◽  
Whole Cell Current

Carbon monoxide (CO) has been postulated to be a messenger in the gastrointestinal tract. The aims of this study were to determine the distribution of heme oxygenase (HO), the source for endogenous CO in the canine jejunum, and to determine the effects of CO on jejunal circular smooth muscle cells. HO-2 isoform was present in a population of myenteric and submucosal neuronal cell bodies, in nerve fibers innervating the muscle layers, and in smooth muscle cells. HO-1 isozyme was not detected in the canine jejunum. Exogenous CO increased whole cell current by 285 ± 86%, hyperpolarized the membrane potential by 8.5 ± 2.9 mV, and increased guanosine 3′,5′-cyclic monophosphate (cGMP) levels in smooth muscle cells. 8-Bromo- cGMP also increased the whole cell current. The data suggest that endogenous activity of HO-2 may be a source of CO in the canine jejunum and that exogenously applied CO can modulate intestinal smooth muscle electrical activity. It is therefore reasonable to suggest a role for endogenously produced CO as a messenger in the canine jejunum.

Thrombin Prevents the Expression of Inducible Nitric Oxide Synthase in Vascular Smooth Muscle Cells by a Proteolytically-Activated Thrombin Receptor

1995 ◽  
Vol 74 (03) ◽  
pp. 980-986 ◽  
Author(s):  
Valérie B Schini-Kerth ◽  
Beate Fißithaler ◽  
Thomas T Andersen ◽  
John W Fenton ◽  
Paul M Vanhoutte ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Inducible Nitric Oxide Synthase ◽  
Muscle Cells ◽  
Thrombin Receptor ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

SummaryProteolytically active forms of thrombin (α- and γ-thrombin) and thrombin receptor peptides inhibited the release of nitrite, a stable endproduct of nitric oxide, evoked by interleukin-1 β(IL-1 β) in cultured vascular smooth muscle cells while proteolytically inactive forms [D-Phe-Pro-Arg chloromethyl ketone-α-thrombin (PPACK-α- thrombin) and diisopropylphosphoryl-α-thrombin (DIP-α-thrombin)] had either no or only minimal inhibitory effects. Under bioassay conditions, perfusates from columns containing IL-1 β-activated vascular smooth muscle cells or cells treated with IL-1βplus PPACK-α-thrombin relaxed detector blood vessels. These relaxations were abolished by the inhibitor of nitric oxide synthesis, NG-nitro-L arginine. No relaxations were obtained with untreated cells or IL-1 β-treated cells in the presence of α-thrombin. The expression of inducible nitric oxide synthase mRNA and protein in vascular smooth muscle cells by IL-1 β was impaired by α-thrombin. These results demonstrate that thrombin regulates the expression of the inducible nitric oxide synthase at a transcriptional level via the proteolytic activation of the thrombin receptor in vascular smooth muscle cells

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