BMC Physiology最新文献

{"title":"Monitoring the wild black bear's reaction to human and environmental stressors.","authors":"Timothy G Laske,&nbsp;David L Garshelis,&nbsp;Paul A Iaizzo","doi":"10.1186/1472-6793-11-13","DOIUrl":"https://doi.org/10.1186/1472-6793-11-13","url":null,"abstract":"<p><strong>Background: </strong>Bears are among the most physiologically remarkable mammals. They spend half their life in an active state and the other half in a state of dormancy without food or water, and without urinating, defecating, or physical activity, yet can rouse and defend themselves when disturbed. Although important data have been obtained in both captive and wild bears, long-term physiological monitoring of bears has not been possible until the recent advancement of implantable devices.</p><p><strong>Results: </strong>Insertable cardiac monitors that were developed for use in human heart patients (Reveal® XT, Medtronic, Inc) were implanted in 15 hibernating bears. Data were recovered from 8, including 2 that were legally shot by hunters. Devices recorded low heart rates (pauses of over 14 seconds) and low respiration rates (1.5 breaths/min) during hibernation, dramatic respiratory sinus arrhythmias in the fall and winter months, and elevated heart rates in summer (up to 214 beats/min (bpm)) and during interactions with hunters (exceeding 250 bpm). The devices documented the first and last day of denning, a period of quiescence in two parturient females after birthing, and extraordinary variation in the amount of activity/day, ranging from 0 (winter) to 1084 minutes (summer). Data showed a transition toward greater nocturnal activity in the fall, preceding hibernation. The data-loggers also provided evidence of the physiological and behavioral responses of bears to our den visits to retrieve the data.</p><p><strong>Conclusions: </strong>Annual variations in heart rate and activity have been documented for the first time in wild black bears. This technique has broad applications to wildlife management and physiological research, enabling the impact of environmental stressors from humans, changing seasons, climate change, social interactions and predation to be directly monitored over multiple years.</p>","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":"11 ","pages":"13"},"PeriodicalIF":0.0,"publicationDate":"2011-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6793-11-13","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30084514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Receptors and effects of gut hormones in three osteoblastic cell lines.","authors":"Elda L Pacheco-Pantoja,&nbsp;Lakshminarayan R Ranganath,&nbsp;James A Gallagher,&nbsp;Peter J M Wilson,&nbsp;William D Fraser","doi":"10.1186/1472-6793-11-12","DOIUrl":"https://doi.org/10.1186/1472-6793-11-12","url":null,"abstract":"<p><strong>Background: </strong>In recent years the interest on the relationship of gut hormones to bone processes has increased and represents one of the most interesting aspects in skeletal research. The proportion of bone mass to soft tissue is a relationship that seems to be controlled by delicate and subtle regulations that imply \"cross-talks\" between the nutrient intake and tissues like fat. Thus, recognition of the mechanisms that integrate a gastrointestinal-fat-bone axis and its application to several aspects of human health is vital for improving treatments related to bone diseases. This work analysed the effects of gut hormones in cell cultures of three osteoblastic cell lines which represent different stages in osteoblastic development. Also, this is the first time that there is a report on the direct effects of glucagon-like peptide 2, and obestatin on osteoblast-like cells.</p><p><strong>Methods: </strong>mRNA expression levels of five gut hormone receptors (glucose-dependent insulinotropic peptide [GIP], glucagon-like peptide 1 [GLP-1], glucagon-like peptide 2 [GLP-2], ghrelin [GHR] and obestatin [OB]) were analysed in three osteoblastic cell lines (Saos-2, TE-85 and MG-63) showing different stages of osteoblast development using reverse transcription and real time polymerase chain reaction. The responses to the gut peptides were studied using assays for cell viability, and biochemical bone markers: alkaline phosphatase (ALP), procollagen type 1 amino-terminal propeptides (P1NP), and osteocalcin production.</p><p><strong>Results: </strong>The gut hormone receptor mRNA displayed the highest levels for GIP in Saos-2 and the lowest levels in MG-63, whereas GHR and GPR39 (the putative obestatin receptor) expression was higher in TE-85 and MG-63 and lower in Saos-2. GLP-1 and GLP-2 were expressed only in MG-63 and TE-85. Treatment of gut hormones to cell lines showed differential responses: higher levels in cell viability in Saos-2 after GIP, in TE-85 and MG-63 after GLP-1, GLP-2, ghrelin and obestatin. ALP showed higher levels in Saos-2 after GIP, GHR and OB and in TE-85 after GHR. P1NP showed higher levels after GIP and OB in Saos-2. Decreased levels of P1NP were observed in TE-85 and MG-63 after GLP-1, GLP-2 and OB. MG-63 showed opposite responses in osteocalcin levels after GLP-2.</p><p><strong>Conclusions: </strong>These results suggest that osteoblast activity modulation varies according to different development stage under different nutrition related-peptides.</p>","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":"11 ","pages":"12"},"PeriodicalIF":0.0,"publicationDate":"2011-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6793-11-12","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30042698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of Caenorhabditis elegans vitellogenesis by DAF-2/IIS through separable transcriptional and posttranscriptional mechanisms.","authors":"Ana S DePina,&nbsp;Wendy B Iser,&nbsp;Sung-Soo Park,&nbsp;Stuart Maudsley,&nbsp;Mark A Wilson,&nbsp;Catherine A Wolkow","doi":"10.1186/1472-6793-11-11","DOIUrl":"https://doi.org/10.1186/1472-6793-11-11","url":null,"abstract":"<p><strong>Background: </strong>Evolutionary theories of aging propose that longevity evolves as a competition between reproduction and somatic maintenance for a finite pool of resources. Reproduction is thought to shorten lifespan by depleting resources from processes promoting somatic maintenance. Maternal yolk production, vitellogenesis, represents a significant maternal cost for reproduction and is suppressed under genetic and environmental conditions that extend lifespan. However, little is known about the pathways regulating vitellogenesis in response to prolongevity cues.</p><p><strong>Results: </strong>In order to identify mechanisms that suppress vitellogenesis under prolongevity conditions, we studied factors regulating vitellogenesis in C. elegans nematodes. In C. elegans, vitellogenesis is depressed in the absence of insulin-like signaling (IIS). We found that the C. elegans daf-2/IIS pathway regulates vitellogenesis through two mechanisms. vit-2 transcript levels in daf-2 mutants were indirectly regulated through a germline-dependent signal, and could be rescued by introduction of daf-2(+) sperm. However, yolk protein (YP) levels in daf-2 mutants were also regulated by germline-independent posttranscriptional mechanisms.</p><p><strong>Conclusions: </strong>C. elegans vitellogenesis is regulated transcriptionally and posttranscriptionally in response to environmental and reproductive cues. The daf-2 pathway suppressed vitellogenesis through transcriptional mechanisms reflecting reproductive phenotypes, as well as distinct posttranscriptional mechanisms. This study reveals that pleiotropic effects of IIS pathway mutations can converge on a common downstream target, vitellogenesis, as a mechanism to modulate longevity.</p>","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":"11 ","pages":"11"},"PeriodicalIF":0.0,"publicationDate":"2011-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6793-11-11","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29856326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The actions of exogenous leucine on mTOR signalling and amino acid transporters in human myotubes.","authors":"Petra Gran,&nbsp;David Cameron-Smith","doi":"10.1186/1472-6793-11-10","DOIUrl":"https://doi.org/10.1186/1472-6793-11-10","url":null,"abstract":"<p><strong>Background: </strong>The branched-chain amino acid (BCAA) leucine has been identified to be a key regulator of skeletal muscle anabolism. Activation of anabolic signalling occurs via the mammalian target of rapamycin (mTOR) through an undefined mechanism. System A and L solute carriers transport essential amino acids across plasma membranes; however it remains unknown whether an exogenous supply of leucine regulates their gene expression. The aim of the present study was to investigate the effects of acute and chronic leucine stimulation of anabolic signalling and specific amino acid transporters, using cultured primary human skeletal muscle cells.</p><p><strong>Results: </strong>Human myotubes were treated with leucine, insulin or co-treated with leucine and insulin for 30 min, 3 h or 24 h. Activation of mTOR signalling kinases were examined, together with putative nutrient sensor human vacuolar protein sorting 34 (hVps34) and gene expression of selected amino acid transporters. Phosphorylation of mTOR and p70S6K was transiently increased following leucine exposure, independently to insulin. hVps34 protein expression was also significantly increased. However, genes encoding amino acid transporters were differentially regulated by insulin and not leucine.</p><p><strong>Conclusions: </strong>mTOR signalling is transiently activated by leucine within human myotubes independently of insulin stimulation. While this occurred in the absence of changes in gene expression of amino acid transporters, protein expression of hVps34 increased.</p>","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":"11 ","pages":"10"},"PeriodicalIF":0.0,"publicationDate":"2011-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6793-11-10","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29961331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regional expression of HOXA4 along the aorta and its potential role in human abdominal aortic aneurysms.","authors":"John H Lillvis, Robert Erdman, Charles M Schworer, Alicia Golden, Kimberly Derr, Zoran Gatalica, Laura A Cox, Jianbin Shen, Richard S Vander Heide, Guy M Lenk, Leigh Hlavaty, Li Li, James R Elmore, David P Franklin, John L Gray, Robert P Garvin, David J Carey, Wayne D Lancaster, Gerard Tromp, Helena Kuivaniemi","doi":"10.1186/1472-6793-11-9","DOIUrl":"10.1186/1472-6793-11-9","url":null,"abstract":"<p><strong>Background: </strong>The infrarenal abdominal aorta exhibits increased disease susceptibility relative to other aortic regions. Allograft studies exchanging thoracic and abdominal segments showed that regional susceptibility is maintained regardless of location, suggesting substantial roles for embryological origin, tissue composition and site-specific gene expression.</p><p><strong>Results: </strong>We analyzed gene expression with microarrays in baboon aortas, and found that members of the HOX gene family exhibited spatial expression differences. HOXA4 was chosen for further study, since it had decreased expression in the abdominal compared to the thoracic aorta. Western blot analysis from 24 human aortas demonstrated significantly higher HOXA4 protein levels in thoracic compared to abdominal tissues (P < 0.001). Immunohistochemical staining for HOXA4 showed nuclear and perinuclear staining in endothelial and smooth muscle cells in aorta. The HOXA4 transcript levels were significantly decreased in human abdominal aortic aneurysms (AAAs) compared to age-matched non-aneurysmal controls (P < 0.00004). Cultured human aortic endothelial and smooth muscle cells stimulated with INF-γ (an important inflammatory cytokine in AAA pathogenesis) showed decreased levels of HOXA4 protein (P < 0.0007).</p><p><strong>Conclusions: </strong>Our results demonstrated spatial variation in expression of HOXA4 in human aortas that persisted into adulthood and that downregulation of HOXA4 expression was associated with AAAs, an important aortic disease of the ageing population.</p>","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":"11 ","pages":"9"},"PeriodicalIF":0.0,"publicationDate":"2011-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3125234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30204993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-endothelial endothelin counteracts hypoxic vasodilation in porcine large coronary arteries.","authors":"Elise R Hedegaard,&nbsp;Edgaras Stankevicius,&nbsp;Ulf Simonsen,&nbsp;Ole Fröbert","doi":"10.1186/1472-6793-11-8","DOIUrl":"https://doi.org/10.1186/1472-6793-11-8","url":null,"abstract":"<p><strong>Background: </strong>The systemic vascular response to hypoxia is vasodilation. However, reports suggest that the potent vasoconstrictor endothelin-1 (ET-1) is released from the vasculature during hypoxia. ET-1 is reported to augment superoxide anion generation and may counteract nitric oxide (NO) vasodilation. Moreover, ET-1 was proposed to contribute to increased vascular resistance in heart failure by increasing the production of asymmetric dimethylarginine (ADMA). We investigated the role of ET-1, the NO pathway, the potassium channels and radical oxygen species in hypoxia-induced vasodilation of large coronary arteries.</p><p><strong>Results: </strong>In prostaglandin F2α (PGF2α, 10 μM)-contracted segments with endothelium, gradual lowering of oxygen tension from 95 to 1% O2 resulted in vasodilation. The vasodilation to O2 lowering was rightward shifted in segments without endothelium at all O2 concentrations except at 1% O2. The endothelin receptor antagonist SB217242 (10 μM) markedly increased hypoxic dilation despite the free tissue ET-1 concentration in the arterial wall was unchanged in 1% O2 versus 95% O2. Exogenous ET-1 reversed hypoxic dilation in segments with and without endothelium, and the hypoxic arteries showed an increased sensitivity towards ET-1 compared to the normoxic controls. Without affecting basal NO, hypoxia increased NO concentration in PGF2α-contracted arteries, and an NO synthase inhibitor, L-NOARG,(300 μM, NG-nitro-L-Arginine) reduced hypoxic vasodilation. NO-induced vasodilation was reduced in endothelin-contracted preparations. Arterial wall ADMA concentrations were unchanged by hypoxia. Blocking of potassium channels with TEA (tetraethylammounium chloride)(10 μM) inhibited vasodilation to O2 lowering as well as to NO. The superoxide scavenger tiron (10 μM) and the putative NADPH oxidase inhibitor apocynin (10 μM) leftward shifted concentration-response curves for O2 lowering without changing vasodilation to 1% O2. PEG (polyethylene glycol) catalase (300 u/ml) inhibited H2O2 vasodilation, but failed to affect vasodilation to O2 lowering. Neither did PEG-SOD (polyethylene glycol superoxide dismutase)(70 u/ml) affect vasodilation to O2 lowering. The mitochondrial inhibitors rotenone (1 μM) and antimycin A (1 μM) both inhibited hypoxic vasodilatation.</p><p><strong>Conclusion: </strong>The present results in porcine coronary arteries suggest NO contributes to hypoxic vasodilation, probably through K channel opening, which is reversed by addition of ET-1 and enhanced by endothelin receptor antagonism. These latter findings suggest that endothelin receptor activation counteracts hypoxic vasodilation.</p>","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":"11 1","pages":"8"},"PeriodicalIF":0.0,"publicationDate":"2011-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6793-11-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29885288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of human amyloid precursor protein in the skeletal muscles of Drosophila results in age- and activity-dependent muscle weakness.","authors":"Chul Kim, Sapeckshita Srivastava, Marian Rice, Tanja A Godenschwege, Brooke Bentley, Saranya Ravi, Shuang Shao, Craig T Woodard, Lawrence M Schwartz","doi":"10.1186/1472-6793-11-7","DOIUrl":"10.1186/1472-6793-11-7","url":null,"abstract":"<p><strong>Background: </strong>One of the hallmarks of Alzheimer's disease, and several other degenerative disorders such as Inclusion Body Myositis, is the abnormal accumulation of amyloid precursor protein (APP) and its proteolytic amyloid peptides. To better understand the pathological consequences of inappropriate APP expression on developing tissues, we generated transgenic flies that express wild-type human APP in the skeletal muscles, and then performed anatomical, electrophysiological, and behavioral analysis of the adults.</p><p><strong>Results: </strong>We observed that neither muscle development nor animal longevity was compromised in these transgenic animals. However, human APP expressing adults developed age-dependent defects in both climbing and flying. We could advance or retard the onset of symptoms by rearing animals in vials with different surface properties, suggesting that human APP expression-mediated behavioral defects are influenced by muscle activity. Muscles from transgenic animals did not display protein aggregates or structural abnormalities at the light or transmission electron microscopic levels. In agreement with genetic studies performed with developing mammalian myoblasts, we observed that co-expression of the ubiquitin E3 ligase Parkin could ameliorate human APP-induced defects.</p><p><strong>Conclusions: </strong>These data suggest that: 1) ectopic expression of human APP in fruit flies leads to age- and activity-dependent behavioral defects without overt changes to muscle development or structure; 2) environmental influences can greatly alter the phenotypic consequences of human APP toxicity; and 3) genetic modifiers of APP-induced pathology can be identified and analyzed in this model.</p>","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":"11 ","pages":"7"},"PeriodicalIF":0.0,"publicationDate":"2011-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3112101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29837093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"JAK/STAT signaling and human in vitro myogenesis.","authors":"Marissa K Trenerry,&nbsp;Paul A Della Gatta,&nbsp;David Cameron-Smith","doi":"10.1186/1472-6793-11-6","DOIUrl":"https://doi.org/10.1186/1472-6793-11-6","url":null,"abstract":"<p><strong>Background: </strong>A population of satellite cells exists in skeletal muscle. These cells are thought to be primarily responsible for postnatal muscle growth and injury-induced muscle regeneration. The Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling cascade has a crucial role in regulating myogenesis. In rodent skeletal muscle, STAT3 is essential for satellite cell migration and myogenic differentiation, regulating the expression of myogenic factors. The aim of the present study was to investigate and compare the expression profile of JAK/STAT family members, using cultured primary human skeletal muscle cells.</p><p><strong>Results: </strong>Near confluent proliferating myoblasts were induced to differentiate for 1, 5 or 10 days. During these developmental stages, members of the JAK/STAT family were examined, along with factors known to regulate myogenesis. We demonstrate the phosphorylation of JAK1 and STAT1 only during myoblast proliferation, while JAK2 and STAT3 phosphorylation increases during differentiation. These increases were correlated with the upregulation of genes associated with muscle maturation and hypertrophy.</p><p><strong>Conclusions: </strong>Taken together, these results provide insight into JAK/STAT signaling in human skeletal muscle development, and confirm recent observations in rodents.</p>","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":"11 ","pages":"6"},"PeriodicalIF":0.0,"publicationDate":"2011-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6793-11-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29727912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fatigue-inducing stimulation resolves myotonia in a drug-induced model.","authors":"Erik van Lunteren,&nbsp;Sarah E Spiegler,&nbsp;Michelle Moyer","doi":"10.1186/1472-6793-11-5","DOIUrl":"https://doi.org/10.1186/1472-6793-11-5","url":null,"abstract":"<p><strong>Background: </strong>Slowed muscle relaxation is the contractile hallmark of myotonia congenita, a disease caused by genetic CLC-1 chloride channel deficiency, which improves with antecedent brief contractions (\"warm-up phenomenon\"). It is unclear to what extent the myotonia continues to dissipate during continued repetitive contractions and how this relates temporally to muscle fatigue. Diaphragm, EDL, and soleus muscles were examined in vitro during repetitive 20 Hz and 50 Hz train stimulation in a drug-induced (9-AC) rat myotonia model.</p><p><strong>Results: </strong>At the onset of stimulation, 9-AC treated diaphragm and EDL muscle had markedly prolonged half relaxation and late relaxation times (range 147 to 884 ms, 894 to 1324 ms). Half relaxation and late relaxation times reached near-normal values over the 5-10 and 10-40 subsequent contractions, respectively. In both muscles myotonia declined faster during repetitive 50 Hz than 20 Hz stimulation, and much faster than the rate of force loss during fatigue at both frequencies. Soleus muscle was resistant to the myotonic effects of 9-AC.</p><p><strong>Conclusions: </strong>In a drug-induced model of mechanical myotonia, fatigue-inducing stimulation resolves the myotonia, which furthermore appears to be independent from the development of muscle fatigue.</p>","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":"11 ","pages":"5"},"PeriodicalIF":0.0,"publicationDate":"2011-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6793-11-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29701127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sodium selectivity of Reissner's membrane epithelial cells.","authors":"Muneharu Yamazaki,&nbsp;Kyunghee X Kim,&nbsp;Daniel C Marcus","doi":"10.1186/1472-6793-11-4","DOIUrl":"https://doi.org/10.1186/1472-6793-11-4","url":null,"abstract":"<p><strong>Background: </strong>Sodium absorption by Reissner's membrane is thought to contribute to the homeostasis of the volume of cochlear endolymph. It was previously shown that the absorptive transepithelial current was blocked by amiloride and benzamil. The most commonly-observed target of these drugs is the epithelial sodium channel (ENaC), which is composed of the three subunits α-,β- and γ-ENaC. However, other less-selective cation channels have also been observed to be sensitive to benzamil and amiloride. The aim of this study was to determine whether Reissner's membrane epithelial cells could support parasensory K+ absorption via amiloride- and benzamil-sensitive electrogenic pathways.</p><p><strong>Results: </strong>We determined the molecular and functional expression of candidate cation channels with gene array (GEO GSE6196), RT-PCR, and whole-cell patch clamp. Transcript expression analysis of Reissner's membrane detected no amiloride-sensitive acid-sensing ion channels (ASIC1a, ASIC2a, ASIC2b) nor amiloride-sensitive cyclic-nucleotide gated channels (CNGA1, CNGA2, CNGA4, CNGB3). By contrast, α-,β- and γ-ENaC were all previously reported as present in Reissner's membrane. The selectivity of the benzamil-sensitive cation currents was observed in whole-cell patch clamp recordings under Cl--free conditions where cations were the only permeant species. The currents were carried by Na+ but not K+, and the permeability of Li+ was greater than that of Na+ in Reissner's membrane. Complete replacement of bath Na+ with the inpermeable cation NMDG+ led to the same inward current as with benzamil in a Na+ bath.</p><p><strong>Conclusions: </strong>These results are consistent with the amiloride/benzamil-sensitive absorptive flux of Reissner's membrane mediated by a highly Na+-selective channel that has several key characteristics in common with αβγ-ENaC. The amiloride-sensitive pathway therefore absorbs only Na+ in this epithelium and does not provide a parasensory K+ efflux route from scala media.</p>","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":"11 ","pages":"4"},"PeriodicalIF":0.0,"publicationDate":"2011-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6793-11-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29640490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}