scholarly journals Adaptive behavior of bacterial mechanosensitive channels is coupled to membrane mechanics

2010 ◽  
Vol 135 (6) ◽  
pp. 641-652 ◽  
Author(s):  
Vladislav Belyy ◽  
Kishore Kamaraju ◽  
Bradley Akitake ◽  
Andriy Anishkin ◽  
Sergei Sukharev
Keyword(s):  
Adaptive Behavior ◽  
Time Course ◽  
Prolonged Exposure ◽  
Mechanosensitive Channel ◽  
Membrane Mechanics ◽  
Response Curves ◽  
Channel Opening ◽  
Complex Adaptive ◽  
Excised Patches ◽  
Pressure Adaptation

Mechanosensitive channel of small conductance (MscS), a tension-driven osmolyte release valve residing in the inner membrane of Escherichia coli, exhibits a complex adaptive behavior, whereas its functional counterpart, mechanosensitive channel of large conductance (MscL), was generally considered nonadaptive. In this study, we show that both channels exhibit similar adaptation in excised patches, a process that is completely separable from inactivation prominent only in MscS. When a membrane patch is held under constant pressure, adaptation of both channels is manifested as a reversible current decline. Their dose–response curves recorded with 1–10-s ramps of pressure are shifted toward higher tension relative to the curves measured with series of pulses, indicating decreased tension sensitivity. Prolonged exposure of excised patches to subthreshold tensions further shifts activation curves for both MscS and MscL toward higher tension with similar magnitude and time course. Whole spheroplast MscS recordings performed with simultaneous imaging reveal activation curves with a midpoint tension of 7.8 mN/m and the slope corresponding to ∼15-nm2 in-plane expansion. Inactivation was retained in whole spheroplast mode, but no adaptation was observed. Similarly, whole spheroplast recordings of MscL (V23T mutant) indicated no adaptation, which was present in excised patches. MscS activities tried in spheroplast-attached mode showed no adaptation when the spheroplasts were intact, but permeabilized spheroplasts showed delayed adaptation, suggesting that the presence of membrane breaks or edges causes adaptation. We interpret this in the framework of the mechanics of the bilayer couple linking adaptation of channels in excised patches to the relaxation of the inner leaflet that is not in contact with the glass pipette. Relaxation of one leaflet results in asymmetric redistribution of tension in the bilayer that is less favorable for channel opening.

scholarly journals Adaptive Behavior of Bacterial Mechanosensitive Channels in Excised Patches is Coupled to Membrane Mechanics

2009 ◽  
Vol 96 (3) ◽  
pp. 256a ◽  
Author(s):  
Vladislav Belyy ◽  
Kishore Kamaraju ◽  
Bradley Akitake ◽  
Andriy Anishkin ◽  
Sergei Sukharev
Keyword(s):  
Adaptive Behavior ◽  
Mechanosensitive Channels ◽  
Membrane Mechanics ◽  
Excised Patches

scholarly journals Complex Adaptive Behavior: Pragmatic Idealism

2016 ◽  
Vol 95 ◽  
pp. 73-79 ◽  
Author(s):  
Mustafa Canan ◽  
Andres Sousa-Poza
Keyword(s):  
Adaptive Behavior ◽  
Complex Adaptive

Spatial perception changes associated with space flight: Implications for adaptation to altered inertial environments

2003 ◽  
Vol 13 (4-6) ◽  
pp. 331-343
Author(s):  
Donald E. Parker
Keyword(s):  
Time Course ◽  
Prolonged Exposure ◽  
Spatial Perception ◽  
Current Knowledge ◽  
Landing Site ◽  
Complete Understanding ◽  
Counter Measures ◽  
Ground Support ◽  
Site Evaluation ◽  
Adaptation Processes

Preparation for extended travel by astronauts within the Solar System, including a possible manned mission to Mars, requires more complete understanding of adaptation to altered inertial environments. Improved understanding is needed to support development and evaluation of interventions to facilitate adaptations during transitions between those environments. Travel to another planet escalates the adaptive challenge because astronauts will experience prolonged exposure to microgravity before encountering a novel gravitational environment. This challenge would have to be met without ground support at the landing site. Evaluation of current adaptive status as well as intervention efficacy can be performed using perceptual, eye movement and postural measures. Due to discrepancies of adaptation magnitude and time-course among these measures, complete understanding of adaptation processes, as well as intervention evaluation, requires examination of all three. Previous research and theory that provide models for comprehending adaptation to altered inertial environments are briefly examined. Reports from astronauts of selected pre- in- and postflight self-motion illusions are described. The currently controversial tilt-translation reinterpretation hypothesis is reviewed and possible resolutions to the controversy are proposed. Finally, based on apparent gaps in our current knowledge, further research is proposed to achieve a more complete understanding of adaptation as well as to develop effective counter-measures.

scholarly journals Distinct Mg2+-dependent Steps Rate Limit Opening and Closing of a Single CFTR Cl− Channel

2002 ◽  
Vol 119 (6) ◽  
pp. 545-559 ◽  
Author(s):  
Athanasios G. Dousmanis ◽  
Angus C. Nairn ◽  
David C. Gadsby
Keyword(s):  
Open Channel ◽  
Tight Binding ◽  
Single Channels ◽  
Channel Opening ◽  
Subsequent Exposure ◽  
Cl Channels ◽  
Excised Patches ◽  
Atp Binding And Hydrolysis ◽  
Opening And Closing ◽  
Rate Limit

The roles played by ATP binding and hydrolysis in the complex mechanisms that open and close cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channels remain controversial. In this work, the contributions made by ATP and Mg2+ ions to the gating of phosphorylated cardiac CFTR channels were evaluated separately by measuring the rates of opening and closing of single channels in excised patches exposed to solutions in which [ATP] and [Mg2+] were varied independently. Channel opening was found to be rate-limited not by the binding of ATP alone, but by a Mg2+-dependent step that followed binding of both ATP and Mg2+. Once a channel had opened, sudden withdrawal of all Mg2+ and ATP could prevent it from closing for tens of seconds. But subsequent exposure of such an open channel to Mg2+ ions alone could close it, and the closing rate increased with [Mg2+] over the micromolar range (half maximal at ∼50 μM [Mg2+]). A simple interpretation is that channel closing is stoichiometrically coupled to hydrolysis of an ATP molecule that remains tightly associated with the open CFTR channel despite continuous washing. If correct, that ATP molecule appears able to reside for over a minute in the catalytic site that controls channel closing, implying that the site must entrap, or have an intrinsically high apparent affinity for, ATP, even without a Mg2+ ion. Such stabilization of the open-channel conformation of CFTR by tight binding, or occlusion, of an ATP molecule echoes the stabilization of the active conformation of a G protein by GTP.

scholarly journals Electrostatic Interaction of Internal Mg2+ with Membrane PIP2 Seen with KCNQ K+ Channels

2007 ◽  
Vol 130 (3) ◽  
pp. 241-256 ◽  
Author(s):  
Byung-Chang Suh ◽  
Bertil Hille
Keyword(s):  
Time Course ◽  
Inhibitory Effects ◽  
Response Curves ◽  
Pipette Solution ◽  
Current Time ◽  
Kv7 Channels ◽  
Cellular Processes ◽  
Polyvalent Cations ◽  
Voltage Dependent ◽  
Phosphatidylinositol 4

Activity of KCNQ (Kv7) channels requires binding of phosphatidylinositol 4,5-bisphosphate (PIP2) from the plasma membrane. We give evidence that Mg2+ and polyamines weaken the KCNQ channel–phospholipid interaction. Lowering internal Mg2+ augmented inward and outward KCNQ currents symmetrically, and raising Mg2+ reduced currents symmetrically. Polyvalent organic cations added to the pipette solution had similar effects. Their potency sequence followed the number of positive charges: putrescine (+2) < spermidine (+3) < spermine (+4) < neomycin (+6) < polylysine (≫+6). The inhibitory effects of Mg2+ were reversible with sequential whole-cell patching. Internal tetraethylammonium ion (TEA) gave classical voltage-dependent block of the pore with changes of the time course of K+ currents. The effect of polyvalent cations was simpler, symmetric, and without changes of current time course. Overexpression of phosphatidylinositol 4-phosphate 5-kinase Iγ to accelerate synthesis of PIP2 attenuated the sensitivity to polyvalent cations. We suggest that Mg2+ and other polycations reduce the currents by electrostatic binding to the negative charges of PIP2, competitively reducing the amount of free PIP2 available for interaction with channels. The dose–response curves could be modeled by a competition model that reduces the pool of free PIP2. This mechanism is likely to modulate many other PIP2-dependent ion channels and cellular processes.

scholarly journals Initial Inoculum and the Severity of COVID-19: A Mathematical Modeling Study of the Dose-Response of SARS-CoV-2 Infections

Epidemiologia ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. 5-15
Author(s):  
Baylor Fain ◽  
Hana M. Dobrovolny
Keyword(s):  
Dose Response ◽  
Time Course ◽  
Severe Disease ◽  
Equation Model ◽  
Viral Titer ◽  
Response Curves ◽  
Agent Based ◽  
Initial Inoculum ◽  
Peak Viral Load ◽  
Titer Curve

SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) causes a variety of responses in those who contract the virus, ranging from asymptomatic infections to acute respiratory failure and death. While there are likely multiple mechanisms triggering severe disease, one potential cause of severe disease is the size of the initial inoculum. For other respiratory diseases, larger initial doses lead to more severe outcomes. We investigate whether there is a similar link for SARS-CoV-2 infections using the combination of an agent-based model (ABM) and a partial differential equation model (PDM). We use the model to examine the viral time course for different sizes of initial inocula, generating dose-response curves for peak viral load, time of viral peak, viral growth rate, infection duration, and area under the viral titer curve. We find that large initial inocula lead to short infections, but with higher viral titer peaks; and that smaller initial inocula lower the viral titer peak, but make the infection last longer.

Effect of cocaine and methylecgonidine on intracellular Ca2+ and myocardial contraction in cardiac myocytes

1997 ◽  
Vol 273 (2) ◽  
pp. H893-H901 ◽  
Author(s):  
L. Huang ◽  
J. H. Woolf ◽  
Y. Ishiguro ◽  
J. P. Morgan
Keyword(s):  
Structural Damage ◽  
Time Course ◽  
Crack Cocaine ◽  
Pyrolysis Product ◽  
Myocardial Contraction ◽  
Dependent Manner ◽  
Response Curves ◽  
Inotropic Effects ◽  
Cell Shortening ◽  
Dose Dependent

We evaluated the cardiac effects of the principle pyrolysis product of crack cocaine smoking, methylecgonidine (MEG), in comparison with cocaine. Peak cell shortening and intracellular Ca2+, as detected by the Ca2+ indicator indo 1, were recorded in enzymatically isolated ferret myocytes. Both cocaine and MEG decreased peak cell shortening and peak intracellular Ca2+ concentration ([Ca2+]i) in a dose-dependent manner (10(-8)-10(-4) M). MEG shifted the peak [Ca2+]i-to-peak shortening relationship downward and was more potent than cocaine. Atropine (10(-6) M) upwardly shifted the dose-response curves of MEG, cocaine, and carbachol but not of procaine. The negative inotropic effects of MEG were inhibited by methoctramine, a selective M2 receptor blocker but not by M1 (pirenzepine) or M3 (4-diphenylacetoxy-N-methylpiperidine methiodide) blocking agents. In contrast to cocaine, the effects of large doses of MEG were irreversible over the time course of our experiments, raising the possibility of structural damage. We conclude that MEG acts primarily on M2 cholinergic receptors in the heart to produce acute cardiac intoxication and, in contrast to cocaine, may decrease the myofilament Ca2+ responseness and cause structural damage to myocytes by a direct toxic effect.

scholarly journals Effect of chronic hypercapnia on body temperature regulation

1975 ◽  
Vol 38 (5) ◽  
pp. 900-906 ◽  
Author(s):  
K. E. Schaefer ◽  
A. A. Messier ◽  
C. Morgan ◽  
G. T. Baker
Keyword(s):  
Body Temperature ◽  
Guinea Pigs ◽  
Time Course ◽  
Prolonged Exposure ◽  
Respiratory Acidosis ◽  
Serotonin Content ◽  
Regulatory Processes ◽  
Transient Rise ◽  
Acid Base Status ◽  
Partial Compensation

Guinea pigs and rats exposed to 15% CO2 for 7 days showed a parallel time course of changes in pH, body temperature (TB), and oxygen consumption (VO2). Between 1 and 6 h of exposure the maximal drop in actual pH occurred in guinea pigs simultaneously with the maximal fall in TB and VO2. During the subsequent period pH TB, VO2 rose again. Skin blood content (heat loss) also exhibited a biphasic pH-dependent time course. Animals showing no partial compensation of respiratory acidosis during 3 days exposure also failed in raising their TB back to normal in this time. The behavior of TB was found to be a good indicator of the acid-base status and adaptive potential of the animals to hypercapnia. Similar results were obtained in rats. Thermo-regulatory processes in the hypothalamus were affected during exposure to 15% CO2. Both guinea pigs and rats showed a decrease in norepinephrine content of the hypothalamus during the first part of exposure reaching a maximal fall at the end of 24 h. The serotonin content increased slightly during this period. During prolonged exposure to 3% CO2 for 7 days, TB showed a transient rise, and VO2 was slightly elevated.

scholarly journals Endothelial dysfunction in human hand veins is rapidly reversible after smoking cessation

1998 ◽  
Vol 275 (3) ◽  
pp. H1040-H1045 ◽  
Author(s):  
Heitor Moreno ◽  
Stephan Chalon ◽  
Akinori Urae ◽  
Oranee Tangphao ◽  
Ademola K. Abiose ◽  
...  
Keyword(s):  
Smoking Cessation ◽  
Endothelial Dysfunction ◽  
Cigarette Smoking ◽  
Time Course ◽  
Human Hand ◽  
Adrenergic Agonist ◽  
Response Curves ◽  
Dorsal Hand ◽  
Time Course Study ◽  
Dorsal Hand Vein

Cigarette smoking has been shown to impair endothelium-dependent dilation in arteries. We tested the hypothesis that cigarette smoking also impairs endothelium-dependent venodilation and evaluated changes in this response after smoking cessation in a time-course study using the dorsal hand vein technique. Dose-response curves were constructed in smokers and nonsmokers by infusing bradykinin (1–278 ng/min), an endothelium-dependent vasodilator, and nitroglycerin (0.006–1,583 ng/min), an endothelium-independent vasodilator, into hand veins preconstricted with the selective α1-adrenergic agonist phenylephrine. The maximal venodilation induced by bradykinin was 89 ± 5% in controls ( n = 16) and 61 ± 7% in smokers ( n = 18; P = 0.02). No difference in nitroglycerin-induced venodilation was observed between the two groups. Coinfusion of l-arginine (0.33 mg/min) markedly improved the bradykinin-induced venodilation in smokers (52 ± 7 to 90 ± 9%; P < 0.01). After acute smoking cessation ( n = 7), restoration to normal bradykinin-induced venodilation was observed within 24 h, whereas no change in the response to a maximally effective dose of nitroglycerin (1,583 ng/min) was detected. In a human vein model appropriate for testing vascular functional alterations, this study demonstrates that smoking impairs endothelium-dependent venodilation in heavy smokers. Moreover, this endothelial dysfunction appears to be rapidly reversible after smoking cessation. This model may be useful in studies evaluating mechanisms of endothelial dysfunction and interventions to modify it.

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