scholarly journals Dynamic expression of homeostatic ion channels in differentiated cortical astrocytes in vitro

2021 ◽  
Author(s):  
Francesco Formaggio ◽  
Martina Fazzina ◽  
Raúl Estévez ◽  
Marco Caprini ◽  
Stefano Ferroni
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Defined Medium ◽  
Culture Conditions ◽  
Membrane Properties ◽  
Cortical Astrocytes ◽  
Cultured Astrocytes ◽  
Functional Features ◽  
Primary Cultured Astrocytes

AbstractThe capacity of astrocytes to adapt their biochemical and functional features upon physiological and pathological stimuli is a fundamental property at the basis of their ability to regulate the homeostasis of the central nervous system (CNS). It is well known that in primary cultured astrocytes, the expression of plasma membrane ion channels and transporters involved in homeostatic tasks does not closely reflect the pattern observed in vivo. The individuation of culture conditions that promotes the expression of the ion channel array found in vivo is crucial when aiming at investigating the mechanisms underlying their dynamics upon various physiological and pathological stimuli. A chemically defined medium containing growth factors and hormones (G5) was previously shown to induce the growth, differentiation, and maturation of primary cultured astrocytes. Here we report that under these culture conditions, rat cortical astrocytes undergo robust morphological changes acquiring a multi-branched phenotype that develop gradually during the 2-week period of culturing. The shape changes were paralleled by variations in passive membrane properties and background conductance owing to the differential temporal development of inwardly rectifying chloride (Cl−) and potassium (K+) currents. Confocal and immunoblot analyses showed that morphologically differentiated astrocytes displayed a robust increase in the expression of the inward rectifier Cl− and K+ channels ClC-2 and Kir4.1, respectively, which are relevant ion channels in vivo. Finally, they exhibited a large diminution of the intermediate filaments glial fibrillary acidic protein (GFAP) and vimentin which are upregulated in reactive astrocytes in vivo. Taken together the data indicate that long-term culturing of cortical astrocytes in this chemical-defined medium promotes a quiescent functional phenotype. This culture model could aid to address the regulation of ion channel expression involved in CNS homeostasis in response to physiological and pathological challenges.

149 EFFECTS OF FSH ADDED IN DEFINED MEDIUM MATURATION ON THE PRE-IMPLANTATION DEVELOPMENT AND EXPRESSION OF Bax, Bcl-2, AND CONNEXIN 43 GENES IN BOVINE IVP BLASTOCYSTS

2010 ◽  
Vol 22 (1) ◽  
pp. 233
Author(s):  
L. V. M. Gulart ◽  
L. Gabriel ◽  
L. P. Salles ◽  
G. R. Gamas ◽  
D. K. Souza ◽  
...  
Keyword(s):  
Internal Control ◽  
Connexin 43 ◽  
Calf Serum ◽  
Defined Medium ◽  
Culture Conditions ◽  
Cleavage Rate ◽  
Embryo Production ◽  
Blastocyst Rate

FSH at low concentrations affect embryo production. In vitro culture conditions also affect embryo production and embryonic expression of genes and alter oocyte competence to produce embryos. The search for better and less variable culture conditions simulating those in vivo has led to the development of several systems of oocyte in vitro maturation culture. To compare the efficiency of the systems of MIV we utilized 4 groups: (1) TCM-199 control; (2) α-minimal essential medium (MEM); 3) α-MEM + 1 ng of FSH; 4) α-MEM+ 10 ng of FSH. The medium of Group 1 is non-defined by the presence of fetal calf serum (10%). Groups 2, 3, and 4 are defined and polyvinyl alcohol (1%) was used as a macromolecule. Porcine FSH (1 IU mg-1) was used at 1 and 10 ng mL-1 and at 100 ng in defined and non-defined medium, respectively. Bovine ovaries were collected at an abbatoir. Oocytes (n = 1718) with homogeneous cytoplasm and with more than 3 layers of granulosa cells were used. Mature oocytes from the 4 treatments (11 replicates of each treatment) were inseminated with frozen-thawed, motile sperm separated by Percoll, using Sperm TALP HEPES medium. Presumptive zygotes with up to 2 or 3 layers of cumulus cells were cultured in 50-mL drops of SOF medium, supplemented with 10% FCS and 1 mg mL-1 BSA under mineral oil in a humid 5% CO2 atmosphere at 38.5°C after. Cleavage rate was evaluated 72 h post-insemination (hpi), and blastocyst rate was evaluated 168-192 hpi. Cleavage and blastocyst rates were calculated on the basis of number of presumptive zygotes. The expression of the following genes (Bax, Bcl-2, and conexin 43) was evaluated in blastocysts by RT-PCR. One-way ANOVA was used to compare blastocyst number. There was no difference in the proportion of embryos with more than 8 blastomeres in all groups tested, indicating that the rate of development during the first 72 hpi was similar for oocytes matured in chemically defined medium and for oocytes matured in medium containing serum. Bax is a pro-apoptotic marker and Bcl-2 an antiapoptotic marker. Connexin 43 (Cx43) may be a marker of embryo competence. Glyceraldehyde 3-phosphate dehydrogenase was used as internal control. The Bax gene was not expressed in any group. The Bcl-2 and Cx43 genes were expressed, mainly in the α-MEM 10. Although no differences were observed in blastocyst rate among the groups (30% to 40%), the strong expression of Bcl-2 and of Cx43 on the group containing 10 ng mL-1 of FSH may indicate that FSH could improve embryo quality under defined conditions. The authors thank FAP-DF, CNPq, FUNPE, FINATEC, CAPES, and Biovitro Tecnologia de Embrioes Ltda, for laboratory assistance and grants, and Frigorifico Ponte Alta, Brasília-DF, for supplying bovine ovaries.

scholarly journals OSCA/TMEM63 are an evolutionarily conserved family of mechanically activated ion channels

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Swetha E Murthy ◽  
Adrienne E Dubin ◽  
Tess Whitwam ◽  
Sebastian Jojoa-Cruz ◽  
Stuart M Cahalan ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Ion Channels ◽  
Ion Channel ◽  
Molecular Mechanisms ◽  
Deep Insight ◽  
Evolutionarily Conserved ◽  
Bona Fide ◽  
Physical Forces ◽  
Insight Into

Mechanically activated (MA) ion channels convert physical forces into electrical signals, and are essential for eukaryotic physiology. Despite their importance, few bona-fide MA channels have been described in plants and animals. Here, we show that various members of the OSCA and TMEM63 family of proteins from plants, flies, and mammals confer mechanosensitivity to naïve cells. We conclusively demonstrate that OSCA1.2, one of the Arabidopsis thaliana OSCA proteins, is an inherently mechanosensitive, pore-forming ion channel. Our results suggest that OSCA/TMEM63 proteins are the largest family of MA ion channels identified, and are conserved across eukaryotes. Our findings will enable studies to gain deep insight into molecular mechanisms of MA channel gating, and will facilitate a better understanding of mechanosensory processes in vivo across plants and animals.

Carfilzomib-Induced Hypertension Is Mediated By Ion Channel Dysregulation in the Kidneys; The Potent Role of AMP-Activated Kinase α

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 34-35
Author(s):  
Panagiotis Efentakis ◽  
Sofia Lamprou ◽  
Polyzois Dimas ◽  
Constantinos Dimitriou ◽  
Manousos Makridakis ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Ion Channels ◽  
Ion Channel ◽  
Board Of Directors ◽  
Research Funding ◽  
Collecting Duct ◽  
Histological Evaluation ◽  
Advisory Committees ◽  
Induced Hypertension

Introduction: Carfilzomib (Cfz), an irreversible proteasome inhibitor (PI), is an approved agent against relapsed/refractory multiple myeloma (R/R MM). Cfz is associated with high incidence of cardiovascular adverse effects. Hypertension stands as the most frequent cardiovascular complication of Cfz. Even though thrombotic microangiopathy (TMA) is inculpated of Cfz's hypertensive phenotype, its exact pathophysiology is still elusive. In our previous work, we showed that Cfz establishes cardiotoxicity in vivo in a Protein Phosphatase 2A (PP2A)-AMP-activated kinase α (AMPKα)-dependent manner (Efentakis P et al. Blood. 2019;133(7):710-723) but does not lead to a permanent vascular deficit, indicating that hypertension is not vascular derived [Efentakis P et al. IJMS 2020;21(15):E5185]. Taking under consideration that renal homeostasis plays an important role in blood pressure regulation we sought to (i) characterize the dose-dependent manifestation of Cfz-induced hypertension; (ii) investigate the molecular signaling of Cfz in the kidneys by proteomic and immunoblotting analyses and (iii) study the renal ion channels regulation. Methods: Forty C57Bl/6 mice (12-14 weeks of age) were randomly assigned to: (i) Acute Protocol: a. Control [Normal Saline (N/S) 0.9%] and b. Cfz (8mg/kg) for two days and (ii) Sub-acute Protocol: a) Control (N/S 0.9%,) and b) Cfz (8mg/kg) for seven days. Intraperitoneal administration of N/S 0.9% and Cfz was performed at two consecutive and on alternate days for the acute and sub-acute protocols respectively. At baseline and endpoint of the experiments, systolic (SBP) and diastolic blood pressure (DBP) were measured, and subsequently mice were sacrificed for the collection of blood and renal samples. Blood samples were collected in citrate buffer for hematological/coagulation profiling [prothrombin time (PT) and INR estimation] and for cleaved Von Willebrand Factor (cl. VWF) immunoblotting assessment as well as for blood testing of white blood cells (WBCs) and platelets. Renal samples underwent histological proteomic and molecular analyses. Results: SBP and DBP were found to be elevated in Cfz group only in the sub-acute protocol compared to control (SBP: 78.5±2.0 vs 68.2±0.7, p<0.01 and DBP: 104.1±2.3 vs 97.4±2.4, p<0.05, respectively). Neutrophil count in the whole blood was elevated both in the acute and sub-acute protocols, while platelet count was decreased in the acute protocol and restored after sub-acute Cfz administration. Mice presented a thrombotic phenotype characterized by increased PT and INR and decreased cl. VWF after acute Cfz treatment, and a hemorrhagic phenotype with restored cl. VWF after sub-acute Cfz administration. However, the presence of TMA was not confirmed by histological evaluation of the kidneys in any of the protocols. Nonetheless histological evaluation of the kidneys revealed inflammation of the perirenal adipose tissue only in the sub-acute protocol. Proteomic analysis presented that proteasome regulation, metabolism and transport of organic anion processes are affected by Cfz administration. Molecular analysis of the renal tissue showed that Cfz induced an increase in the inducible nitric oxide synthase (iNOS) and microtubule-associated proteins 1A/1B light chain 3B (LC3-B) expression and a decreased AMPKα phosphorylation. Moreover, RT-PCR analysis of the renal samples revealed that collecting duct ion channels epithelial Na+ channel (ENaC), Na+/K+/ATPase and urea transporter 1 (UTA-1) mRNA levels were increased in Cfz group. Conclusion: Sub-acute Cfz treatment establishes a renal-derived hypertensive phenotype and a circulating inflammatory phenotype as indicated by the increased neutrophil and WBCs count in the blood. TMA does not seem to be implicated with the observed phenotype in vivo as investigated molecularly and histologically. Cfz-induced dephosphorylation of AMPKα and the subsequent dysregulation of the collecting duct renal ion channel homeostasis is found to be responsible for the observed effect. Therefore, Cfz seems to induce hypertension by a dysregulation of water-ion re-absorbance leading to increased cardiac preload. The latter comes in agreement with clinical data showing that some Cfz-treated patients present with fluid retention, which can be attributed to the aforementioned renal effects of the drug. Disclosures Efentakis: Amgen: Research Funding. Kastritis:Amgen: Consultancy, Honoraria, Research Funding; Genesis Pharma: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria. Dimopoulos:BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau. Andreadou:Amgen: Research Funding. Terpos:Amgen: Honoraria, Research Funding; Genesis pharma SA: Honoraria, Other: travel expenses , Research Funding; Janssen: Honoraria, Research Funding; Takeda: Honoraria, Other: travel expenses , Research Funding; Celgene: Honoraria; Sanofi: Honoraria; BMS: Honoraria.

scholarly journals Fuel Cell Using Squid Axon Electrolyte and Its Proton Conductivity

2020 ◽  
Vol 11 (4) ◽  
pp. 86
Author(s):  
Tomoki Furuseki ◽  
Yasumitsu Matsuo
Keyword(s):  
Fuel Cell ◽  
Ion Channels ◽  
Ion Channel ◽  
Power Density ◽  
Proton Conductivity ◽  
Clean Energy ◽  
Squid Axon ◽  
High Proton Conductivity ◽  
High Proton

Fuel cells using biomaterials have the potential for environmentally friendly clean energy and have attracted a lot of interest. Moreover, biomaterials are expected to develop into in vivo electrical devices such as pacemakers with no side effects. Ion channels, which are membrane proteins, are known to have a fast ion transport capacity. Therefore, by using ion channels, the realization of fuel cell electrolytes with high-proton conductivity can be expected. In this study, we have fabricated a fuel cell using an ion channel electrolyte for the first time and investigated the electrical properties of the ion channel electrolyte. It was found that the fuel cell using the ion channel membrane shows a power density of 0.78 W/cm2 in the humidified condition. On the other hand, the power density of the fuel cell blocking the ion channel with the channel blocker drastically decreased. These results indicate that the fuel cell using the ion channel electrolyte operates through the existence of the ion channel and that the ion channel membrane can be used as the electrolyte of the fuel cell in humidified conditions. Furthermore, the proton conductivity of the ion channel electrolyte drastically increases above 85% relative humidity (RH) and becomes 2 × 10−2 S/m at 96% RH. This result indicates that the ion channel becomes active above 96%RH. In addition, it was deduced from the impedance analysis that the high proton conductivity of the ion channel electrolyte above 96% RH is caused by the activation of ion channels, which are closely related to the fractionalization of water molecule clusters. From these results, it was found that a fuel cell using the squid axon becomes a new fuel cell using the function of the ion channel above 96% RH.

scholarly journals Neonatal cortical astrocytes possess intrinsic potential in neuronal conversion in defined media

2021 ◽  
Author(s):  
Peng Zeng ◽  
Qiu-hong Hua ◽  
Jun-yuan Gong ◽  
Chang-jie Shi ◽  
Xiao-ping Pi ◽  
...  
Keyword(s):  
Detailed Comparison ◽  
Brain Regions ◽  
Culture Conditions ◽  
Neuronal Markers ◽  
Electrophysiological Properties ◽  
Neuronal Progenitor ◽  
Cortical Astrocytes ◽  
The Central Nervous System ◽  
And Function

AbstractAstrocytes are multifunctional brain cells responsible for maintaining the health and function of the central nervous system. Accumulating evidence suggests that astrocytes might be complementary source across different brain regions to supply new neurons during adult neurogenesis. In this study, we found that neonatal mouse cortical astrocytes can be directly converted into neurons when exposed to neurogenic differentiation culture conditions, with insulin being the most critical component. Detailed comparison studies between mouse cortical astrocytes and neuronal progenitor cells (NPCs) demonstrated the converted neuronal cells originate indeed from the astrocytes rather than NPCs. The neurons derived from mouse cortical astrocytes display typical neuronal morphologies, express neuronal markers and possess typical neuronal electrophysiological properties. More importantly, these neurons can survive and mature in the mouse brain in vivo. Finally, by comparing astrocytes from different brain regions, we found that only cortical astrocytes but not astrocytes from other brain regions such as hippocampus and cerebellum can be converted into neurons under the current condition. Altogether, our findings suggest that neonatal astrocytes from certain brain regions possess intrinsic potential to differentiate/transdifferentiate into neurons which may have clinical relevance in the future.

Effect of embryo developmental stage and culture conditions on number and quality of ovine in vitro produced blastocysts

Zygote ◽  
2006 ◽  
Vol 14 (3) ◽  
pp. 181-187 ◽  
Author(s):  
R.M. Garcia-Garcia ◽  
V. Dominguez ◽  
A. Gonzalez-Bulnes ◽  
A. Veiga-Lopez ◽  
M.J. Cocero
Keyword(s):  
Developmental Stage ◽  
Developmental Stages ◽  
Developmental Rate ◽  
Defined Medium ◽  
Culture Conditions ◽  
Cell Groups ◽  
Early Developmental

SummaryThis study evaluated the final output and quality of in vitro produced blastocysts derived from in vivo recovered sheep embryos cultured at various early developmental stages to blastocyst. A total of 270 embryos were recovered from the oviduct, at different days of the early luteal phase, and were classified into three different developmental stages: 2- to 4-cell (n = 93); 5- to 8-cell (n = 92) and 9- to 12-cell (n = 85). The effect of culture conditions was studied, at the same time, by randomly allocating the embryos to one of four groups: three groups of culture with fresh oviduct monolayers (2, 4 and 5 days old) and a fourth group with 2-day monolayers derived from frozen-thawed oviduct cells. Two control groups were established: first, embryos cultured in semi-defined medium (n = 29) and, second, blastocysts obtained in vivo and cryopreserved (n = 43). Influence on blastocyst yield of embryo developmental stage at the start of culture was statistically significant (p < 0.001). Two- to four-cell embryos showed a significantly lower developmental rate (67.7%) than the 5- to 8-cell (83.6%; p < 0.001) and 9- to 12-cell groups (90.5%; p < 0.0001) and lower quality in terms of blastocyst cryotolerance (56.0 vs. 83.7%; p < 0.005). There were no detected effects relating to the age or handling of the monolayer on the embryo developmental rate, but the day of blastocyst appearance was different between embryos cultured on monolayers derived from fresh or frozen-thawed cells (p < 0.0001); the main influence was on the group of 9- to 12-cell embryos (p < 0.0001). Current results confirm the temporal sensitivities of sheep embryos to in vitro culture, regardless of the culture conditions.

scholarly journals Identification of dividing, determined sensory neuron precursors in the mammalian neural crest

Development ◽  
1999 ◽  
Vol 126 (16) ◽  
pp. 3545-3559
Author(s):  
A.L. Greenwood ◽  
E.E. Turner ◽  
D.J. Anderson
Keyword(s):  
Transcription Factors ◽  
Neural Crest ◽  
Sensory Neurons ◽  
Large Diameter ◽  
Defined Medium ◽  
Culture Conditions ◽  
Helix Loop Helix ◽  
Pou Domain ◽  
Bhlh Transcription Factors

Sensory and autonomic neurons of the vertebrate peripheral nervous system are derived from the neural crest. Here we use the expression of lineage-specific transcription factors as a means to identify neuronal subtypes that develop in rat neural crest cultures grown in a defined medium. Sensory neurons, identified by expression of the POU-domain transcription factor Brn-3.0, develop from dividing precursors that differentiate within 2 days following emigration from the neural tube. Most of these precursors generate sensory neurons even when challenged with BMP2, a factor that induces autonomic neurogenesis in many other cells in the explants. Moreover, BMP2 fails to prevent expression of the sensory-specific basic helix-loop-helix (bHLH) transcription factors neurogenin1, neurogenin2 and neuroD, although it induces expression of the autonomic-specific bHLH factor MASH1 and the paired homeodomain factor Phox2a in other cells. These data suggest that there are mitotically active precursors in the mammalian neural crest that can generate sensory neurons even in the presence of a strong autonomic-inducing cue. Further characterization of the neurons generated from such precursors indicates that, under these culture conditions, they exhibit a proprioceptive and/or mechanosensory, but not nociceptive, phenotype. Such precursors may therefore correspond to a lineally (Frank, E. and Sanes, J. (1991) Development 111, 895–908) and genetically (Ma, Q., Fode, C., Guillemot, F. and Anderson, D. J. (1999) Genes Dev. 13, in press) distinct subset of early-differentiating precursors of large-diameter sensory neurons identified in vivo.

scholarly journals Functional pangenome analysis suggests inhibition of the protein E as a readily available therapy for COVID-2019

2020 ◽  
Author(s):  
Intikhab alam ◽  
Allan Kamau ◽  
Maxat Kulmanov ◽  
Stefan T. Arold ◽  
Arnab Pain ◽  
...  
Keyword(s):  
Ion Channel ◽  
Viral Entry ◽  
Neutralizing Antibodies ◽  
Protein S ◽  
Gene Clusters ◽  
Core Gene ◽  
Host Cells ◽  
Binding Motif ◽  
Functional Features

AbstractThe spread of the novel coronavirus (SARS-CoV-2) has triggered a global emergency, that demands urgent solutions for detection and therapy to prevent escalating health, social and economic impacts. The spike protein (S) of this virus enables binding to the human receptor ACE2, and hence presents a prime target for vaccines preventing viral entry into host cells1. The S proteins from SARS-CoV-1 and SARS-CoV-2 are similar2, but structural differences in the receptor binding domain (RBD) preclude the use of SARS-CoV-1–specific neutralizing antibodies to inhibit SARS-CoV-23. Here we used comparative pangenomic analysis of all sequenced Betacoronaviruses to reveal that, among all core gene clusters present in these viruses, the envelope protein E shows a variant shared by SARS and SARS-Cov2 with two completely-conserved key functional features, an ion-channel and a PDZ-binding Motif (PBM). These features trigger a cytokine storm that activates the inflammasome, leading to increased edema in lungs causing the acute respiratory distress syndrome (ARDS)4-6, the leading cause of death in SARS-CoV-1 and SARS-CoV-2 infection7,8. However, three drugs approved for human use may inhibit SARS-CoV-1 and SARS-CoV-2 Protein E, either acting upon the ion channel (Amantadine and Hexamethylene amiloride9,10) or the PBM (SB2035805), thereby potentially increasing the survival of the host, as already demonstrated for SARS-CoV-1in animal models. Hence, blocking the SARS protein E inhibits development of ARDS in vivo. Given that our results demonstrate that the protein E subcluster for the SARS clade is quasi-identical for the key functional regions of SARS-CoV-1 and SARS-CoV-2, we conclude that use of approved drugs shown to act as SARS E protein inhibitors can help prevent further casualties from COVID-2019 while vaccines and other preventive measures are being developed.

scholarly journals Mining recent brain proteomic databases for ion channel phosphosite nuggets

2010 ◽  
Vol 137 (1) ◽  
pp. 3-16 ◽  
Author(s):  
Oscar Cerda ◽  
Je-Hyun Baek ◽  
James S. Trimmer
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Mammalian Brain ◽  
Phosphorylation Sites ◽  
Dynamic Regulation ◽  
Voltage Gated ◽  
Voltage Gated Ion Channels ◽  
Α Subunits

Voltage-gated ion channels underlie electrical activity of neurons and are dynamically regulated by diverse cell signaling pathways that alter their phosphorylation state. Recent global mass spectrometric–based analyses of the mouse brain phosphoproteome have yielded a treasure trove of new data as to the extent and nature of phosphorylation of numerous ion channel principal or α subunits in mammalian brain. Here we compile and review data on 347 phosphorylation sites (261 unique) on 42 different voltage-gated ion channel α subunits that were identified in these recent studies. Researchers in the ion channel field can now begin to explore the role of these novel in vivo phosphorylation sites in the dynamic regulation of the localization, activity, and expression of brain ion channels through multisite phosphorylation of their principal subunits.

scholarly journals Swapping of transmembrane domains in the epithelial calcium channel TRPV6

2017 ◽  
Author(s):  
Appu K. Singh ◽  
Kei Saotome ◽  
Alexander I. Sobolevsky
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Calcium Channel ◽  
Transmembrane Domain ◽  
Transmembrane Domains ◽  
Domain Swapping ◽  
Structural Determinants ◽  
Disease States ◽  
Pore Domains

AbstractTetrameric ion channels have either swapped or non-swapped arrangements of the S1-S4 and pore domains. Here we show that mutations in the transmembrane domain of TRPV6 can result in conversion from a domain-swapped to non-swapped fold. These results reveal structural determinants of domain swapping and raise the possibility that a single ion channel subtype can fold into either arrangement in vivo, affecting its function in normal or disease states.

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