ABSTRACT
A Gram-stain-negative, aerobic, orange-coloured, rod-shaped and non-motile bacterial strain, PAMC 29362T, was isolated from an Antarctic lichen, Megaspora verrucosa. Phylogenetic and phylogenomic analyses indicated that strain PAMC 29362T belongs to the genus Polymorphobacter and was most closely related to Polymorphobacter arshaanensis (97.0% of 16S rRNA gene similarity), Polymorphobacter fuscus (96.3â%), Polymorphobacter multimanifer (95.3â%) and Polymorphobacter glacialis (95.2â%). Genomic relatedness analyses showed that strain PAMC 29362T is clearly distinguished from type strains of the genus Polymorphobacter based on values of average nucleotide identity (<74.3â%) and digital DNA-DNA hybridization (<20.4â%). The genomic DNA G+C content of PAMC 29362T was 65.5â%. The major fatty acids (>10â%) were summed feature 8 (C18:1 ω7c; 38.5â%) and summed feature 3 (C16:1 ω7c and/or C16:1 ω6c; 31.5â%). The major respiratory quinone was Q-10. Based on the results of phylogenetic, genome-based relatedness and physiological analyses, strain PAMC 29362T is proposed to represent a novel species of the genus Polymorphobacter, with the name Polymorphobacter megasporae sp. nov. The type strain is PAMC 29362T (=KCTC 82â578T=JCM 34545T).
Subject(s)
Alphaproteobacteria , Lichens , Alphaproteobacteria/genetics , Bacterial Typing Techniques , Base Composition , DNA, Bacterial/genetics , Fatty Acids/chemistry , Nucleotides , Phospholipids , Phylogeny , Quinones , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNAABSTRACT
Gram-stain-negative, strictly aerobic, red-pink-coloured, rod-shaped and non-motile bacterial strains PAMC 29290, PAMC 29294T and PAMC 29296 were isolated from marine surface sediment sampled in the East Siberian Sea and strains PAMC 26553 and PAMC 26554T were obtained from an Antarctic lichen. Strains PAMC 29290, PAMC 29294T and PAMC 29296 were closely related to Hymenobacter artigasi (98.8â% 16S rRNA gene similarity), Hymenobacter antarcticus (97.3â%) and Hymenobacter glaciei (96.9â%), and PAMC 26553 and PAMC 26554T showed high similarity to Hymenobacter ginsengisoli (97.0â%), Hymenobacter rivuli (96.1â%) and Hymenobacter setariae (95.9â%). Genomic relatedness analyses showed that strains PAMC 29290, PAMC 29294T and PAMC 29296 could be distinguished from H. artigasi by average nucleotide identity (ANI; 93.1-93.2â%) and digital DNA-DNA hybridization (dDDH; 50.3-51.0â%) values. Strains PAMC 26553 and PAMC 26554T could be clearly distinguished from H. ginsengisoli with ANI values <79.8â% and dDDH values <23.3â%. The major fatty acids of strains PAMC 29290, PAMC 29294T and PAMC 29296 were C15â:â0 iso (21.0-26.0â%), summed feature 3 (C16â:â1 ω7c and/or C16â:â1 ω6c; 17.4-18.2â%), C15â:â0 anteiso (12.7-19.1â%) and summed feature 4 (C17â:â1 iso I and/or anteiso B; 8.6-16.1â%) and those of strains PAMC 26553 and PAMC 26554T were summed feature 3 (C16â:â1 ω7c and/or C16â:â1 ω6c; 20.7-22.2â%), C15â:â0 anteiso (17.5-19.7â%) and summed feature 4 (C17â:â1 iso I and/or anteiso B; 15.5-18.1â%). The major respiratory quinone was MK-7. The genomic DNA G+C contents were 60.6-60.8 mol%. The polar lipids of PAMC 29294T were found to consist of phosphatidylethanolamine, four unidentified aminolipids, an unidentified aminophospholipid and five unidentified lipids; those of PAMC 26554T were phosphatidylethanolamine, three unidentified aminolipids, four unidentified aminophospholipid and two unidentified lipids. The distinct phylogenetic position and some physiological characteristics distinguished the novel strains from closely related type strains in the genus Hymenobacter. Thus, two novel species are proposed, with the names Hymenobacter siberiensis sp. nov. (type strain, PAMC 29294T=KCTC 82466T=JCM 34574T) and Hymenobacter psoromatis sp. nov. (type strain, PAMC 26554T=KCTC 82464T=JCM 34572T), respectively.
Subject(s)
Lichens , Bacterial Typing Techniques , Base Composition , DNA, Bacterial/genetics , Fatty Acids/chemistry , Geologic Sediments/microbiology , Phylogeny , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNAABSTRACT
Two Gram-stain-negative, facultative anaerobic, chemoheterotrophic, pink-coloured, rod-shaped and non-motile bacterial strains, PAMC 26568 and PAMC 26569T, were isolated from an Antarctic lichen. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strains PAMC 26568 and PAMC 26569T belong to the family Acetobacteraceae and the most closely related species are Gluconacetobacter takamatsuzukensis (96.1â%), Gluconacetobacter tumulisoli (95.9â%) and Gluconacetobacter sacchari (95.7â%). Phylogenomic and genomic relatedness analyses showed that strains PAMC 26568 and PAMC 26569T are clearly distinguished from other genera in the family Acetobacteraceae by average nucleotide identity values (<72.8â%) and the genome-to-genome distance values (<22.5â%). Genomic analysis revealed that strains PAMC 26568 and PAMC 26569T do not contain genes involved in atmospheric nitrogen fixation and utilization of sole carbon compounds such as methane and methanol. Instead, strains PAMC 26568 and PAMC 26569T possess genes to utilize nitrate and nitrite and certain monosaccharides and disaccharides. The major fatty acids (>10â%) are summed feature 8 (C18â:â1 ω7c and/or C18â:â1 ω6c; 40.3-40.4â%), C18â:â1 2OH (22.7-23.7â%) and summed feature 2 (C14â:â0 3OH and/or C16â:â1 iso I; 12.0â% in PAMC 26568). The major respiratory quinone is Q-10. The genomic DNA G+C content of PAMC 26568 and PAMC 26569T is 64.6â%. Their distinct phylogenetic position and some physiological characteristics distinguish strains PAMC 26568 and PAMC 26569T from other genera in the family Acetobacteraceae supporting the proposal of Lichenicola gen. nov., with the type species Lichenicola cladoniae sp. nov. (type strain, PAMC 26569T=KCCM 43315T=JCM 33604T).
Subject(s)
Acetobacteraceae/classification , Lichens/microbiology , Phylogeny , Acetobacteraceae/isolation & purification , Antarctic Regions , Bacterial Typing Techniques , Base Composition , DNA, Bacterial/genetics , Fatty Acids/chemistry , Pigmentation , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , Ubiquinone/analogs & derivatives , Ubiquinone/chemistryABSTRACT
Two Gram-stain-negative, facultative anaerobic chemoheterotrophic, pink-coloured, rod-shaped and non-motile bacterial strains, PAMC 29128 and PAMC 29148T, were isolated from lichen. Phylogenetic analysis based on the 16S rRNA gene sequences revealed that strains PAMC 29128 and PAMC 29148T belong to lichen-associated Rhizobiales-1 (LAR1), an uncultured phylogenetic lineage of the order Rhizobiales and the most closely related genera were Methylocapsa (<93.9â%) and Methylosinus (<93.8â%). The results of phylogenomic and genomic relatedness analyses also showed that strains PAMC 29128 and PAMC 29148T were clearly distinguished from other species in the order Rhizobiales with average nucleotide identity values of <71.4â% and genome-to-genome distance values of <22.7â%. Genomic analysis revealed that strains PAMC 29128 and PAMC 29148T did not contain genes involved in atmospheric nitrogen fixation or utilization of carbon compounds such as methane and methanol. Strains PAMC 29128 and PAMC 29148T were able to utilize certain monosaccharides, disaccharides, sugar alcohols and other organic compounds as a sole carbon source. The major fatty acids (>10â%) were summed feature 8 (C18â:â1 ω7c and/or C18â:â1 ω6c; 33.7-39.7â%), summed feature 3 (C16â:â1 ω7c and/or C 16:1 ω6c; 25.2-25.4â%) and C19â:0 cyclo ω8c (11.9-15.4â%). The major respiratory quinone was Q-10. The genomic DNA G+C contents of PAMC 29128 and PAMC 29148T were 63.0 and 63.1 mol%, respectively. Their distinct phylogenetic position and some physiological characteristics support the proposal of Lichenihabitans gen. nov., with the type species Lichenihabitans psoromatis sp. nov. (type strain, PAMC 29148T=KCCM 43293T=JCM 33311T). Lichenihabitantaceae fam. nov. is also proposed.
Subject(s)
Alphaproteobacteria/classification , Lichens/microbiology , Phylogeny , Alphaproteobacteria/isolation & purification , Antarctic Regions , Bacterial Typing Techniques , Base Composition , DNA, Bacterial/genetics , Fatty Acids/chemistry , Pigmentation , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , Ubiquinone/analogs & derivatives , Ubiquinone/chemistryABSTRACT
[Purpose] Although much researches have been conducted on the hippotherapy, the intervention methods of the previous studies focus on the pelvis posture. Thus, this study analyzed the electromyogram (EMG) of trunk muscle and lower limb muscle to analyze the kinetic factors. Based on the analysis, this study aims to compare the muscle load and suggest effective exercise method. [Participants and Methods] This study checked the muscle activity of Rectus abdominis (RA), Erector spinae (ES), Rectus femoris (RF), Adductor magnus (AM) during the exercise using horse riding machine in dorsiflexion position by bending 20 degrees and in neutral position. Each position was performed for 5 minutes and the speed of the horse riding machine was set to medium speed. [Results] Rectus abdominis showed higher muscle activity in dorsiflexion position and the groups had significant differences. Elector spinae showed higher muscle activity in dorsiflexion position and the groups had significant differences. Rectus femoris showed higher muscle activity in dorsiflexion position and the groups had significant differences. Adductor magnus also showed higher muscle activity in dorsiflexion position and the groups had significant differences. [Conclusions] The study result showed that exercise with horse riding machine in dorsiflexion position activates trunk muscle and thigh muscle effectively. Thus, the study suggests more effective posture for the modern people who exercise with horse riding machine for strengthening physical health.
ABSTRACT
Ketamine is an anesthetic with hypertensive effects, which make it useful for patients at risk of shock. However, previous ex vivo studies reported vasodilatory actions of ketamine in isolated arteries. In this study, we reexamined the effects of ketamine on arterial tones in the presence and absence of physiological concentrations of 5-hydroxytryptamine (5-HT) and norepinephrine (NE) by measuring the isometric tension of endothelium-denuded rat mesenteric arterial rings. Ketamine little affected the resting tone of control mesenteric arterial rings, but, in the presence of 5-HT (100~200 nM), ketamine (10~100 µM) markedly contracted the arterial rings. Ketamine did not contract arterial rings in the presence of NE (10 nM), indicating that the vasoconstrictive action of ketamine is 5-HT-dependent. The concentration-response curves (CRCs) of 5-HT were clearly shifted to the left in the presence of ketamine (30 µM), whereas the CRCs of NE were little affected by ketamine. The left shift of the 5-HT CRCs caused by ketamine was reversed with ketanserin, a competitive 5-HT2A receptor inhibitor, indicating that ketamine facilitated the activation of 5-HT2A receptors. Anpirtoline and BW723C86, selective agonists of 5-HT1B and 5-HT2B receptors, respectively, did not contract arterial rings in the absence or presence of ketamine. These results indicate that ketamine specifically enhances 5-HT2A receptor-mediated vasoconstriction and that it is vasoconstrictive in a clinical setting. The facilitative action of ketamine on 5-HT2A receptors should be considered in ketamine-induced hypertension as well as in the pathogenesis of diseases such as schizophrenia, wherein experimental animal models are frequently generated using ketamine.
ABSTRACT
Hydrogen peroxide (H2O2) is an endothelium-derived hyperpolarizing factor. Since opposing vasoactive effects have been reported for H2O2 depending on the vascular bed and experimental conditions, this study was performed to assess whether H2O2 acts as a vasodilator in the rat mesenteric artery and, if so, to determine the underlying mechanisms. H2O2 elicited concentration-dependent relaxation in mesenteric arteries precontracted with norepinephrine. The vasodilatory effect of H2O2 was reversed by treatment with dithiothreitol. H2O2-elicited vasodilation was significantly reduced by blocking 4-aminopyridine (4-AP)-sensitive Kv channels, but it was resistant to blockers of big-conductance Ca(2+)-activated K(+) channels and inward rectifier K(+) channels. A patch-clamp study in mesenteric arterial smooth muscle cells (MASMCs) showed that H2O2 increased Kv currents in a concentration-dependent manner. H2O2 speeded up Kv channel activation and shifted steady state activation to hyperpolarizing potentials. Similar channel activation was seen with oxidized glutathione (GSSG). The H2O2-mediated channel activation was prevented by glutathione reductase. Consistent with S-glutathionylation, streptavidin pull-down assays with biotinylated glutathione ethyl ester showed incorporation of glutathione (GSH) in the Kv channel proteins in the presence of H2O2. Interestingly, conditions of increased oxidative stress within MASMCs impaired the capacity of H2O2 to stimulate Kv channels. Not only was the H2O2 stimulatory effect much weaker, but the inhibitory effect of H2O2 was unmasked. These data suggest that H2O2 activates 4-AP-sensitive Kv channels, possibly through S-glutathionylation, which elicits smooth muscle relaxation in rat mesenteric arteries. Furthermore, our results support the idea that the basal redox status of MASMCs determines the response of Kv currents to H2O2.
Subject(s)
Glutathione/metabolism , Hydrogen Peroxide/pharmacology , Muscle, Smooth, Vascular/metabolism , Potassium Channels/metabolism , Vasodilation , 4-Aminopyridine/pharmacology , Action Potentials , Animals , Cells, Cultured , Glutathione Reductase/metabolism , Male , Mesenteric Arteries/cytology , Mesenteric Arteries/metabolism , Mesenteric Arteries/physiology , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/physiology , Potassium Channel Blockers/pharmacology , Rats , Rats, Sprague-DawleyABSTRACT
Fungi are cosmopolitan and they occupy diverse niches as consumers, producers, and decomposers. They play critical roles in the environment by enabling nutrient cycling and generating a plethora of secondary metabolites. This study aimed to identify and characterize fungal strains isolated from diverse sources on Muui Island, Republic of Korea. In 2023, a total of 86 fungal strains were collected and examined. Investigation of the morphological features and phylogenetic analyses of multiple barcode loci identified one putative novel species and two species previously unrecorded in the Republic of Korea: Colletotrichum sp., Colletotrichum guizhouense, and Fusarium brachygibbosum. This study provides a comprehensive description of their molecular phylogenies and morphological characteristics. These findings will contribute to the existing knowledge about fungal species in the Republic of Korea and future research on the fungal diversity on Muui Island.
ABSTRACT
AIMS: Caveolae are invaginated, Ω-shaped membrane structures. They are now recognized as portals for signal transduction of multiple chemical and mechanical stimuli. Notably, the contribution of caveolae has been reported to be receptor-specific. However, details of how they differentially contribute to receptor signaling remain unclear. MAIN METHODS: Using isometric tension measurements, patch-clamping, and western blotting, we examined the contribution of caveolae and their related signaling pathways to serotonergic (5-HT2A receptor-mediated) and adrenergic (α1-adrenoceptor-mediated) signaling in rat mesenteric arteries. KEY FINDINGS: Disruption of caveolae by methyl-ß-cyclodextrin effectively blocked vasoconstriction mediated by the 5-HT2A receptor (5-HT2AR), but not by the α1-adrenoceptor. Caveolar disruption selectively impaired 5-HT2AR-mediated voltage-dependent K+ channel (Kv) inhibition, but not α1-adrenoceptor-mediated Kv inhibition. In contrast, both serotonergic and α1-adrenergic effects on vasoconstriction, as well as Kv currents, were similarly blocked by the Src tyrosine kinase inhibitor PP2. However, inhibition of protein kinase C (PKC) by either GO6976 or chelerythrine selectively attenuated the effects mediated by the α1-adrenoceptor, but not by 5-HT2AR. Disruption of caveolae decreased 5-HT2AR-mediated Src phosphorylation, but not α1-adrenoceptor-mediated Src phosphorylation. Finally, the PKC inhibitor GO6976 blocked Src phosphorylation by the α1-adrenoceptor, but not by 5-HT2AR. SIGNIFICANCE: 5-HT2AR-mediated Kv inhibition and vasoconstriction are dependent on caveolar integrity and Src tyrosine kinase, but not on PKC. In contrast, α1-adrenoceptor-mediated Kv inhibition and vasoconstriction are not dependent on caveolar integrity, but rather on PKC and Src tyrosine kinase. Caveolae-independent PKC is upstream of Src activation for α1-adrenoceptor-mediated Kv inhibition and vasoconstriction.
Subject(s)
Protein Kinase C , src-Family Kinases , Rats , Animals , src-Family Kinases/metabolism , Protein Kinase C/metabolism , Caveolae/metabolism , Adrenergic Agents/metabolism , Adrenergic Agents/pharmacology , Serotonin/pharmacology , Serotonin/metabolism , Vasoconstriction , Receptor, Serotonin, 5-HT2A/metabolism , Protein Kinase Inhibitors/pharmacology , Receptors, Adrenergic/metabolismABSTRACT
The diversity of lichen-associated bacteria from lichen taxa Cetraria, Cladonia, Megaspora, Pseudephebe, Psoroma, and Sphaerophorus was investigated by sequencing of 16S rRNA gene amplicons. Physiological characteristics of the cultured bacterial isolates were investigated to understand possible roles in the lichen ecosystem. Proteobacteria (with a relative abundance of 69.7-96.7%) were mostly represented by the order Rhodospirillales. The 117 retrieved isolates were grouped into 35 phylotypes of the phyla Actinobacteria (27), Bacteroidetes (6), Deinococcus-Thermus (1), and Proteobacteria (Alphaproteobacteria (53), Betaproteobacteria (18), and Gammaproteobacteria (12)). Hydrolysis of macromolecules such as skim milk, polymer, and (hypo)xanthine, solubilization of inorganic phosphate, production of phytohormone indole-3-acetic acid, and fixation of atmospheric nitrogen were observed in different taxa. The potential phototrophy of the strains of the genus Polymorphobacter which were cultivated from a lichen for the first time was revealed by the presence of genes involved in photosynthesis. Altogether, the physiological characteristics of diverse bacterial taxa from Antarctic lichens are considered to imply significant roles of lichen-associated bacteria to allow lichens to be tolerant or competitive in the harsh Antarctic environment.
ABSTRACT
Lichens are miniature ecosystems that contain fungi, microalgae, and bacteria. It is generally accepted that symbiosis between mycobiont and photobiont and microbial contribution to the ecosystem support the wide distribution of lichens in terrestrial ecosystems, including polar areas. The composition of symbiotic components can be affected by subtle microenvironmental differences within a thallus, as well as large-scale climate differences. In this study, we investigated fine-scale profiles of algal, fungal, and bacterial compositions through horizontal and vertical positions of the Antarctic lichen Cladonia squamosa colonies by next-generation sequencing of the nuclear large subunit rRNA gene (nucLSU) of eukaryotes and the 16S rRNA gene of bacteria. Apical parts of thalli were exposed to strong light, low moisture, and high variability of temperature compared with basal parts. Microbial diversity increased from apical parts to basal parts of thalli. Asterochloris erici was the major photobiont in apical positions of thalli, but other microalgal operational taxonomic units (OTUs) of Trebouxiophyceae and Ulvophyceae were major microalgal components in basal positions. Photochemical responses of algal components from apical and basal parts of thalli were quite different under variable temperature and humidity conditions. Several fungal OTUs that belonged to Arthoniomycetes and Lecanoromycetes, and diverse bacterial OTUs that belonged to Alphaproteobacteria, Acidobacteria_Gp1, and candidate division WPS-2 showed a clear distribution pattern according to their vertical positions within thalli. The overall lichen microbiome was significantly differentiated by the vertical position within a thallus. These results imply that different microclimate are formed at different lichen thallus parts, which can affect microbial compositions and physiological responses according to positions within the thalli.
ABSTRACT
Candidate phylum Atribacteria JS1 lineage is one of the predominant bacterial groups in anoxic subseafloor sediments, especially in organic-rich or gas hydrate-containing sediments. However, due to the lack of axenic culture representatives, metabolic potential and biogeochemical roles of this phylum have remained elusive. Here, we examined the microbial communities of marine sediments of the Ross Sea, Antarctica, and found candidate phylum Atribacteria JS1 lineage was the most abundant candidate phylum accounting for 9.8-40.8% of the bacterial communities with a single dominant operational taxonomic unit (OTU). To elucidate the metabolic potential and ecological function of this species, we applied a single-cell genomic approach and obtained 18 single-cell amplified genomes presumably from a single species that was consistent with the dominant OTU throughout the sediments. The composite genome constructed by co-assembly showed the highest genome completeness among available Atribacteria JS1 genomes. Metabolic reconstruction suggested fermentative potential using various substrates and syntrophic acetate oxidation coupled with hydrogen or formate scavenging methanogens. This metabolic potential supports the predominance of Atribacteria JS1 in anoxic environments expanding our knowledge of the ecological function of this uncultivated group.
ABSTRACT
MK801 and ketamine, which are phencyclidine (PCP) derivative N-methyl-d-aspartate receptor (NMDAr) blockers, reportedly enhance the function of 5-hydroxytryptamine (HT)-2A receptors (5-HT2ARs). Both are believed to directly affect the pathogenesis of schizophrenia, as well as hypertension. 5-HT2AR signaling involves the inhibition of Kv conductance. This study investigated the interaction of these drugs with Kv1.5, which plays important roles in 5-HT2AR signaling and in regulating the excitability of the cardiovascular and nervous system, and the potential role of this interaction in the enhancement of the 5-HT2AR-mediated response. Using isometric organ bath experiments with arterial rings and conventional whole-cell patch-clamp recording of Chinese hamster ovary (CHO) cells ectopically overexpressing Kv1.5, we examined the effect of ketamine and MK801 on 5-HT2AR-mediated vasocontraction and Kv1.5 channels. Both ketamine and MK801 potentiated 5-HT2AR-mediated vasocontraction. This potentiation of 5-HT2AR function occurred in a membrane potential-dependent manner, indicating the involvement of ion channel(s). Both ketamine and MK801 rapidly and directly inhibited Kv1.5 channels from the extracellular side independently of NMDArs. The potencies of MK801 in facilitating the 5-HT2AR-mediated response and blocking Kv1.5 were higher than those of ketamine. Our data demonstrated the direct inhibition of Kv1.5 channels by MK801/ketamine and indicated that this inhibition may potentiate the functions of 5-HT2ARs. We suggest that 5-HT2AR-Kv1.5 may serve as a receptor-effector module in response to 5-HT and is a promising target in the pathogenesis of MK801-/ketamine-induced disease states such as hypertension and schizophrenia.
Subject(s)
Dizocilpine Maleate/pharmacology , Ketamine/pharmacology , Kv1.5 Potassium Channel/antagonists & inhibitors , Potassium Channel Blockers/pharmacology , Serotonin 5-HT2 Receptor Agonists/pharmacology , Animals , CHO Cells , Cricetulus , Hypertension/metabolism , Kv1.5 Potassium Channel/metabolism , Male , Patch-Clamp Techniques , Rats, Sprague-Dawley , Receptor, Serotonin, 5-HT2A/metabolism , Schizophrenia/metabolism , Vasoconstrictor Agents/pharmacologyABSTRACT
Although serotonin (5-hydroxytryptamine, 5-HT) has been found to be a potent vasoconstrictor, a pivotal role of 5-HT in the control of appetite and mood control by the modulation of neuronal synapse has also been proposed. Selective 5-HT reuptake inhibitors (SSRIs) are frequently used to suppress appetite and treat depressive disorder, and the target protein of SSRIs is the 5-HT transporter (5-HTT) in the neuronal synapse. However, SSRIs may increase the free 5-HT concentration in circulating blood because platelets and vascular smooth muscles express functional 5-HTT. In addition, enhanced vasoactive action of 5-HT and alterations in 5-HT receptor subtypes have been reported in some types of hypertension. Therefore, we can infer that the use of drugs such as SSRIs in some hypertensive patients is potentially risky. Altered functional expression of ion channels in vascular smooth muscle is suggested to be a mechanism for the enhanced vasoconstriction by vasoactive agonists, including 5-HT. In this brief review, we compared the electrophysiological properties of mesenteric artery myocytes and their modulation by 5-HT between sham-operated control and deoxycorticosterone acetate (DOCA)-salt hypertensive rats.
Subject(s)
Hypertension/chemically induced , Hypertension/physiopathology , Selective Serotonin Reuptake Inhibitors/toxicity , Serotonin/metabolism , Animals , Blood Pressure/drug effects , Desoxycorticosterone , Mesenteric Arteries/drug effects , Rats , Rats, Mutant Strains , Serotonin Plasma Membrane Transport Proteins/metabolism , Sodium Chloride, DietaryABSTRACT
Serotonin (5-hydroxytryptamine (5-HT)) is a neurotransmitter that regulates a variety of functions in the nervous, gastrointestinal and cardiovascular systems. Despite such importance, 5-HT signaling pathways are not entirely clear. We demonstrated previously that 4-aminopyridine (4-AP)-sensitive voltage-gated K(+) (Kv) channels determine the resting membrane potential of arterial smooth muscle cells and that the Kv channels are inhibited by 5-HT, which depolarizes the membranes. Therefore, we hypothesized that 5-HT contracts arteries by inhibiting Kv channels. Here we studied 5-HT signaling and the detailed role of Kv currents in rat mesenteric arteries using patch-clamp and isometric tension measurements. Our data showed that inhibiting 4-AP-sensitive Kv channels contracted arterial rings, whereas inhibiting Ca(2+)-activated K(+), inward rectifier K(+) and ATP-sensitive K(+) channels had little effect on arterial contraction, indicating a central role of Kv channels in the regulation of resting arterial tone. 5-HT-induced arterial contraction decreased significantly in the presence of high KCl or the voltage-gated Ca(2+) channel (VGCC) inhibitor nifedipine, indicating that membrane depolarization and the consequent activation of VGCCs mediate the 5-HT-induced vasoconstriction. The effects of 5-HT on Kv currents and arterial contraction were markedly prevented by the 5-HT2A receptor antagonists ketanserin and spiperone. Consistently, α-methyl 5-HT, a 5-HT2 receptor agonist, mimicked the 5-HT action on Kv channels. Pretreatment with a Src tyrosine kinase inhibitor, 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine, prevented both the 5-HT-mediated vasoconstriction and Kv current inhibition. Our data suggest that 4-AP-sensitive Kv channels are the primary regulator of the resting tone in rat mesenteric arteries. 5-HT constricts the arteries by inhibiting Kv channels via the 5-HT2A receptor and Src tyrosine kinase pathway.