scholarly journals Electrophysiological Characterization of Human Atria: The Understated Role of Temperature

2021 ◽  
Vol 12 ◽  
Author(s):  
Rupamanjari Majumder ◽  
Afnan Nabizath Mohamed Nazer ◽  
Alexander V. Panfilov ◽  
Eberhard Bodenschatz ◽  
Yong Wang
Keyword(s):  
Action Potential ◽  
Ambient Temperature ◽  
Mild Hypothermia ◽  
Signal Propagation ◽  
Resting Membrane Potential ◽  
Influence Of Temperature On ◽  
Electrophysiological Characterization ◽  
Increasing Temperature ◽  
Important Characterization

Ambient temperature has a profound influence on cellular electrophysiology through direct control over the gating mechanisms of different ion channels. In the heart, low temperature is known to favor prolongation of the action potential. However, not much is known about the influence of temperature on other important characterization parameters such as the resting membrane potential (RMP), excitability, morphology and characteristics of the action potential (AP), restitution properties, conduction velocity (CV) of signal propagation, etc. Here we present the first, detailed, systematic in silico study of the electrophysiological characterization of cardiomyocytes from different regions of the normal human atria, based on the effects of ambient temperature (5−50°C). We observe that RMP decreases with increasing temperature. At ~ 48°C, the cells lose their excitability. Our studies show that different parts of the atria react differently to the same changes in temperature. In tissue simulations a drop in temperature correlated positively with a decrease in CV, but the decrease was region-dependent, as expected. In this article we show how this heterogeneous response can provide an explanation for the development of a proarrhythmic substrate during mild hypothermia. We use the above concept to propose a treatment strategy for atrial fibrillation that involves severe hypothermia in specific regions of the heart for a duration of only ~ 200 ms.

Electrophysiological characterization of human atria: the understated role of temperature

2020 ◽  
Author(s):  
Rupamanjari Majumder ◽  
Afnan Nabizath Mohamed Nazer ◽  
Alexander V. Panfilov ◽  
Eberhard Bodenschatz ◽  
Yong Wang
Keyword(s):  
Action Potential ◽  
Ambient Temperature ◽  
Mild Hypothermia ◽  
Signal Propagation ◽  
Resting Membrane Potential ◽  
Influence Of Temperature On ◽  
Normal Human ◽  
Electrophysiological Characterization ◽  
Increasing Temperature

ABSTRACTAmbient temperature has a profound influence on cellular electrophysiology through direct control over the gating mechanisms of different ion channels. In the heart, low temperature is known to favour prolongation of the action potential. However, not much is known about the influence of temperature on other important characterisation parameters such as the resting membrane potential (RMP), excitability, morphology and characteristics of the action potential (AP), restitution properties, conduction velocity (CV) of signal propagation, etc. Here we present the first, detailed, systematic in silico study of the electrophysiological characterization of cardiomyocytes from different regions of the normal human atria, based on the effects of ambient temperature (5 −50°C). We observe that RMP decreases with increasing temperature. At ∼ 48°C, the cells lose their excitability. Our studies show that different parts of the atria react differently to the same changes in temperature. In tissue simulations a drop in temperature correlated positively with a decrease in CV, but the decrease was region-dependent, as expected. In this article we show how this heterogeneous response can provide an explanation for the development of a proarrhythmic substrate during mild hypothermia. We use the above concept to propose a treatment strategy for atrial fibrillation that involves severe hypothermia in specific regions of the heart for a duration of only ∼ 200ms.

Cellular mechanisms of early tachycardia-induced ventricular dysfunction in the human heart

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Knierim ◽  
S Pabel ◽  
M Paulus ◽  
P Rainer ◽  
D Scherr ◽  
...  
Keyword(s):  
Relaxation Time ◽  
Action Potential ◽  
Human Heart ◽  
Time Course ◽  
Ventricular Dysfunction ◽  
Myocardial Dysfunction ◽  
Human Myocardium ◽  
Resting Membrane Potential ◽  
Funding Source

Abstract Background Tachycardia-induced cardiomyopathy (TCM) is a reversible form of ventricular dysfunction caused by persistent tachycardia. Characterization of TCM is mainly based on artificially RV paced animal models. Moreover, the underlying mechanisms and time course from compensation to failure remain unclear. This study aimed to investigate early cellular remodeling of tachycardia-induced myocardial dysfunction in human myocardium. Methods and results To elucidate early cellular electrophysiological targets mediating the transition to TCM, we chronically paced (120bpm vs 60bpm control) human induced pluripotent stem cell cardiomyocytes (hiPS-CM) for up to 7d. As a major substrate of cellular myocardial dysfunction, we investigated the influence of chronic tachycardia on cellular Ca cycling. After 24h of persistent tachycardia we detected a significant decrease in Ca transient (CaT) amplitude and reduced diastolic Ca levels (Fura-2). Meanwhile, Ca elimination time (RT80) was unchanged compared to control (n=44/42 cells / 8 diff.). Caffeine application was performed to evaluate sarcoplasmic reticulum (SR) Ca load. We found a shortening of caffeine-induced CaT relaxation time, whereas SR Ca load was unchanged (n=12/13 /8). Further illustrating the transition to TCM, CaT amplitude was progressively decreased after 7d of chronic tachycardia. In contrast to 24h of tachycardia, 7d persistent stimulation resulted in slowed relaxation (RT80, n=75/65 /7). These findings could be explained by a significant reduction of SERCA activity (Ksys-Kcaff) and SR Ca load (n=14/12 / 7). Diastolic Ca concentration remained reduced (n=75/65 /7), in total suggesting a shift to transsarcolemmal Ca elimination. Sodium measurements (SBFI) revealed a significant increase of intracellular sodium concentration (n=69/69 /5) after 7d of tachycardia. In patch clamp experiments we detected a prolongation of action potential duration as early as 24h after onset of tachycardia (n=26/21 /4), which persisted throughout 7d of pacing (n=8/12 /3). Resting membrane potential and action potential amplitude were not changed. Finally, we investigated tachycardia-mediated effects on pre-existing human heart failure (HF). 8h tachycardic stimulation (120bpm) of human HF ventricular trabeculae compromised systolic force, while diastolic tension and relaxation time were markedly increased compared to control (60bpm) (n=7/6 trabeculae /6 human hearts). The extensive molecular characterization of involved ion channels and pathways mediating transition to TCM is currently under investigation. Conclusion This study demonstrates that a persistent tachycardia adversely alters cardiomyocyte excitation-contraction coupling via early electrophysiological cellular remodeling. In pre-existing HF persistent tachycardia strongly aggravates ventricular dysfunction. Our first translational investigation in human myocardium may help to understand the pathophysiology of an underrated and very prevalent disease. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Else-Kröner-Fresenius-Stiftung

Electrophysiological characterization of murine HL-5 atrial cardiomyocytes

2006 ◽  
Vol 291 (3) ◽  
pp. C407-C416 ◽  
Author(s):  
Yong-Fu Xiao ◽  
Erica M. TenBroek ◽  
Joshua J. Wilhelm ◽  
Paul A. Iaizzo ◽  
Daniel C. Sigg
Keyword(s):  
Action Potentials ◽  
Adult Mouse ◽  
Resting Membrane Potential ◽  
Muscarinic Agonist ◽  
Atrial Cardiomyocytes ◽  
Cation Current ◽  
Whole Cell Patch Clamp ◽  
Electrophysiological Characterization

HL-5 cells are cultured murine atrial cardiomyocytes and have been used in studies to address important cellular and molecular questions. However, electrophysiological features of HL-5 cells have not been characterized. In this study, we examined such properties using whole cell patch-clamp techniques. Membrane capacitance of the HL-5 cells was from 8 to 62 pF. The resting membrane potential was −57.8 ± 1.4 mV ( n = 51). Intracellular injection of depolarizing currents evoked action potentials (APs) with variable morphologies in 71% of the patched cells. Interestingly, the incidence of successful, current-induced APs positively correlated with the hyperpolarizing degrees of resting membrane potentials ( r = 0.99, P < 0.001). Only a few of the patched cells (4 of 51, 7.8%) exhibited spontaneous APs. The muscarinic agonist carbachol activated the acetylcholine-activated K+ current and significantly shortened the duration of APs. Immunostaining confirmed the presence of the muscarinic receptor type 2 in HL-5 cells. The hyperpolarization-activated cation current ( If) was detected in 39% of the patched cells. The voltage to activate 50% of If channels was −73.4 ± 1.2 mV ( n = 12). Voltage-gated Na+, Ca2+, and K+ currents were observed in the HL-5 cells with variable incidences. Compared with the adult mouse cardiomyocytes, the HL-5 cells had prolonged APs and small outward K+ currents. Our data indicate that HL-5 cells display significant electrophysiological heterogeneity of morphological appearance of APs and expression of functional ion channels. Compared with adult murine cardiomyocytes, HL-5 cells show an immature phenotype of cardiac AP morphology.

Crystallographic Characterization of Dislocation Loops in Irradiated Tungsten

1968 ◽  
Vol 26 ◽  
pp. 290-291
Author(s):  
Robert C. Rau
Keyword(s):  
Electron Microscope ◽  
Ambient Temperature ◽  
Dislocation Loops ◽  
Polycrystalline Specimen ◽  
Post Irradiation ◽  
Neutron Fluences

Previous work has shown that post-irradiation annealing, at temperatures near 1100°C, produces resolvable dislocation loops in tungsten irradiated to fast (E > 1 MeV) neutron fluences of about 4 x 1019 n/cm2 or greater. To crystallographically characterize these loops, tilting experiments were carried out in the electron microscope on a polycrystalline specimen which had been irradiated to 1.5 × 1021 n/cm2 at reactor ambient temperature (∼ 70°C), and subseouently annealed for 315 hours at 1100°C. This treatment produced large loops averaging 1000 Å in diameter, as shown in the micrographs of Fig. 1. The orientation of this grain was near (001), and tilting was carried out about axes near [100], [10] and [110].

Electrophysiological Characterization of Transport Across Outer Membrane Channels from Gram-Negative Bacteria in Their Native Environment

2019 ◽  
Author(s):  
Jiajun Wang ◽  
Rémi Terrasse ◽  
Jayesh Arun Bafna ◽  
Lorraine Benier ◽  
Mathias Winterhalter
Keyword(s):  
Outer Membrane ◽  
Lipid Membrane ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Multi Drug Resistance ◽  
Gram Negative Bacteria ◽  
Membrane Channels ◽  
Gram Negative ◽  
Electrophysiological Characterization

Multi-drug resistance in Gram-negative bacteria is often associated with low permeability of the outer membrane. To investigate the role of membrane channels in the uptake of antibiotics, we extract, purify and reconstitute them into artificial planar membranes. To avoid this time-consuming procedure, here we show a robust approach using fusion of native outer membrane vesicles (OMV) into planar lipid bilayer which moreover allows also to some extend the characterization of membrane protein channels in their native environment. Two major membrane channels from <i>Escherichia coli</i>, OmpF and OmpC, were overexpressed from the host and the corresponding OMVs were collected. Each OMV fusion revealed surprisingly single or only few channel activities. The asymmetry of the OMV´s translates after fusion into the lipid membrane with the LPS dominantly present at the side of OMV addition. Compared to conventional reconstitution methods, the channels fused from OMVs containing LPS have similar conductance but a much broader distribution. The addition of Enrofloxacin on the LPS side yields somewhat higher association (<i>k<sub>on</sub></i>) and lower dissociation (<i>k<sub>off</sub></i>) rates compared to LPS-free reconstitution. We conclude that using outer membrane vesicles is a fast and easy approach for functional and structural studies of membrane channels in the native membrane.

scholarly journals Electrophysiological characterization of a diverse group of sugar transporters from Trichoderma reesei

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sami Havukainen ◽  
Jonai Pujol-Giménez ◽  
Mari Valkonen ◽  
Ann Westerholm-Parvinen ◽  
Matthias A. Hediger ◽  
...  
Keyword(s):  
Trichoderma Reesei ◽  
Scientific Literature ◽  
Large Body ◽  
Comprehensive Analysis ◽  
Transport Function ◽  
Sugar Transporters ◽  
New Knowledge ◽  
Electrophysiological Characterization ◽  
Shed Light

AbstractTrichoderma reesei is an ascomycete fungus known for its capability to secrete high amounts of extracellular cellulose- and hemicellulose-degrading enzymes. These enzymes are utilized in the production of second-generation biofuels and T. reesei is a well-established host for their production. Although this species has gained considerable interest in the scientific literature, the sugar transportome of T. reesei remains poorly characterized. Better understanding of the proteins involved in the transport of different sugars could be utilized for engineering better enzyme production strains. In this study we aimed to shed light on this matter by characterizing multiple T. reesei transporters capable of transporting various types of sugars. We used phylogenetics to select transporters for expression in Xenopus laevis oocytes to screen for transport activities. Of the 18 tested transporters, 8 were found to be functional in oocytes. 10 transporters in total were investigated in oocytes and in yeast, and for 3 of them no transport function had been described in literature. This comprehensive analysis provides a large body of new knowledge about T. reesei sugar transporters, and further establishes X. laevis oocytes as a valuable tool for studying fungal sugar transporters.

scholarly journals Electrophysiological characterization of contact sites in brain mitochondria.

1990 ◽  
Vol 265 (2) ◽  
pp. 908-913
Author(s):  
O Moran ◽  
G Sandri ◽  
E Panfili ◽  
W Stühmer ◽  
M C Sorgato
Keyword(s):  
Brain Mitochondria ◽  
Contact Sites ◽  
Electrophysiological Characterization

scholarly journals Insect body size changes under future warming projections: a case study of Chironomidae (Insecta: Diptera)

Hydrobiologia ◽  
2021 ◽  
Author(s):  
Rungtip Wonglersak ◽  
Phillip B. Fenberg ◽  
Peter G. Langdon ◽  
Stephen J. Brooks ◽  
Benjamin W. Price
Keyword(s):  
Body Size ◽  
Ambient Temperature ◽  
Wing Length ◽  
The Body ◽  
Mesocosm Experiments ◽  
Future Warming ◽  
Increasing Temperature ◽  
Emergence Date ◽  
Average Body

AbstractChironomids are a useful group for investigating body size responses to warming due to their high local abundance and sensitivity to environmental change. We collected specimens of six species of chironomids every 2 weeks over a 2-year period (2017–2018) from mesocosm experiments using five ponds at ambient temperature and five ponds at 4°C higher than ambient temperature. We investigated (1) wing length responses to temperature within species and between sexes using a regression analysis, (2) interspecific body size responses to test whether the body size of species influences sensitivity to warming, and (3) the correlation between emergence date and wing length. We found a significantly shorter wing length with increasing temperature in both sexes of Procladius crassinervis and Tanytarsus nemorosus, in males of Polypedilum sordens, but no significant relationship in the other three species studied. The average body size of a species affects the magnitude of the temperature-size responses in both sexes, with larger species shrinking disproportionately more with increasing temperature. There was a significant decline in wing length with emergence date across most species studied (excluding Polypedilum nubeculosum and P. sordens), indicating that individuals emerging later in the season tend to be smaller.

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