Isoflurane activates rat mitochondrial ATP-sensitive K+ channels reconstituted in lipid bilayers

2003 ◽  
Vol 284 (5) ◽  
pp. H1865-H1871 ◽  
Author(s):  
Yuri Nakae ◽  
Wai-Meng Kwok ◽  
Zeljko J. Bosnjak ◽  
Ming Tao Jiang
Keyword(s):  
Lipid Bilayers ◽  
Myocardial Protection ◽  
Volatile Anesthetic ◽  
Volatile Anesthetics ◽  
Open Probability ◽  
Myocardial Preconditioning ◽  
Atp Inhibition ◽  
Conductance States ◽  
Dose Dependent ◽  
Direct Regulation

Activation of mitochondrial ATP-sensitive K+ (mitoKATP) channels is critical in myocardial protection induced by preconditioning with volatile anesthetics or brief periods of ischemia. In this study, we characterized rat mitoKATP channels reconstituted in lipid bilayers and examined their direct regulation by isoflurane. Mitochondria and the inner membrane fraction were isolated from rat ventricles and fused into lipid bilayers. On the basis of their inhibition by 5-hydroxydecanoate (5-HD)/ATP or activation by diazoxide, mitoKATP channels of several conductance states were observed in symmetrical (150 mM) potassium glutamate (26, 47, 66, 83, and 105 pS). Isoflurane (0.8 mM) increased the cumulative open probability from 0.09 ± 0.02 at baseline to 0.50 ± 0.09 ( P < 0.05, n = 5), which was inhibited by 5-HD. Isoflurane caused a dose-dependent rightward shift in ATP inhibition of mitoKATP channels, which increased the IC50 for ATP from 335 ± 4 to 940 ± 34 μM at 0.8 mM ( P < 0.05, n = 5∼8). We conclude that direct activation of the mitoKATP channel by isoflurane is likely to contribute to volatile anesthetic-induced myocardial preconditioning.

Acetaldehyde alters Ca2+-release channel gating and muscle contraction in a dose-dependent manner

2004 ◽  
Vol 286 (5) ◽  
pp. C1188-C1194 ◽  
Author(s):  
Toshiharu Oba ◽  
Yoshitaka Maeno
Keyword(s):  
Lipid Bilayers ◽  
Muscle Force ◽  
Muscle Dysfunction ◽  
Dependent Manner ◽  
Channel Activity ◽  
Open Probability ◽  
Release Channel ◽  
Twitch Potentiation ◽  
Dose Dependent ◽  
Maximum Rate Of Rise

We studied whether acetaldehyde, which is produced by alcohol consumption, impacts ryanodine receptor (RyR) activity and muscle force. Exposure to ∼50–200 μM acetaldehyde enhanced channel activity of frog RyR and rabbit RyR1 incorporated into lipid bilayers. An increase in acetaldehyde to 1 mM modified channel activity in a time-dependent manner, with a brief activation and then inhibition. Application of 200 μM acetaldehyde to frog fibers increased twitch tension. The maximum rate of rise of tetanus tension was accelerated to 1.5 and 1.74 times the control rate on exposure of fibers to 50 and 200 μM acetaldehyde, respectively. Fluorescence monitoring with fluo 3 demonstrated that 200–400 μM acetaldehyde induced Ca2+ release from the sarcoplasmic reticulum (SR) in frog muscles. Acetaldehyde at 1 mM inhibited twitch tension by ∼12%, with an increased relaxation time after a small, transient twitch potentiation. These results suggest that moderate concentrations of acetaldehyde can elicit Ca2+ release from the SR by increasing the open probability of the RyR channel, resulting in increased tension. However, the effects of acetaldehyde at clinical doses (1–30 μM) are unlikely to mediate alcohol-induced acute muscle dysfunction.

scholarly journals Volatile Anesthetic Effects on Midbrain-elicited Locomotion Suggest that the Locomotor Network in the Ventral Spinal Cord Is the Primary Site for Immobility

2008 ◽  
Vol 108 (6) ◽  
pp. 1016-1024 ◽  
Author(s):  
Steven L. Jinks ◽  
Milo Bravo ◽  
Shawn G. Hayes
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Hind Limb ◽  
Volatile Anesthetic ◽  
Volatile Anesthetics ◽  
Step Frequency ◽  
Electrical Microstimulation ◽  
Dorsal Horn Neurons ◽  
Dose Dependent ◽  
Ventral Spinal Cord

Background Volatile anesthetics produce immobility primarily by action in the spinal cord; however, anesthetic effects among different neuronal classes located in different spinal regions, and how they relate to immobility, are not understood. Methods In decerebrated rats, effects of isoflurane and halothane on movement elicited by electrical microstimulation of the mesencephalic locomotor region (MLR) were assessed in relation to minimum alveolar concentration (MAC). Anesthetic effects on step frequency and isometric limb force were measured. The authors also examined effects of MLR stimulation on responses of nociceptive dorsal horn neurons and limb force responses to tail clamp. Results Mean isoflurane requirements to block MLR-elicited stepping were slightly but significantly greater than MAC by 10%. Mean halothane requirements to block MLR-elicited stepping were greater than those for isoflurane and exceeded MAC by 20%. From 0.4 to 1.3 MAC (but not 0.0 to 0.4 MAC), there was a dose-dependent reduction in the frequency and force of hind limb movements elicited by MLR stimulation during both anesthetics. MLR stimulation inhibited noxious stimulus evoked responses of dorsal horn neurons by approximately 80%. Aptly, MLR stimulation produced analgesia that outlasted the midbrain stimulus by at least 15 s, as indicated by an 81% reduction in hind limb force elicited noxious tail clamp. Conclusions Because electrical stimulation of the MLR elicits movement independent of dorsal horn activation, the immobilizing properties of isoflurane and halothane are largely independent of action in the dorsal horn. The results suggest that volatile anesthetics produce immobility mainly by action on ventral spinal locomotor networks.

scholarly journals Total Intravenous Anesthesia for Myocardial Protection and Preconditioning

2021 ◽  
Author(s):  
Minati Choudhury
Keyword(s):  
Protective Effect ◽  
Surgical Procedure ◽  
Myocardial Protection ◽  
Myocardial Injury ◽  
Volatile Anesthetic ◽  
Organ Protection ◽  
Intravenous Anesthesia ◽  
Intravenous Anesthetic ◽  
Anesthetic Agents ◽  
Anesthetic Preconditioning

AbstractPerioperative myocardial injury is common after any major surgical procedure even with best possible anesthesia and surgical management. Organ preservation during surgical procedure prevents morbidity and mortality. The effect of ischemic preconditioning on myocardial as well as other organ protection is well known. A variety of other agents also shown to have preconditioning thus protective effect on myocardium during anesthesia and surgery. The beneficial effect of volatile anesthetic preconditioning is well studied. However, the effect of intravenous anesthetic agents on this context is still way to go. This review is an attempt to look into the latest available research regarding the preconditioning and myocardial protective effect of intravenous anesthetic agents.

Volatile Anesthetics Affect Nutrient Availability in Yeast

Genetics ◽  
2002 ◽  
Vol 161 (2) ◽  
pp. 563-574
Author(s):  
Laura K Palmer ◽  
Darren Wolfe ◽  
Jessica L Keeley ◽  
Ralph L Keil
Keyword(s):  
Amino Acids ◽  
Nutrient Availability ◽  
Wild Type Strain ◽  
Volatile Anesthetic ◽  
Volatile Anesthetics ◽  
Wild Type ◽  
Anesthetic Exposure ◽  
Sites Of Action ◽  
Insight Into ◽  
Lines Of Evidence

Abstract Volatile anesthetics affect all cells and tissues tested, but their mechanisms and sites of action remain unknown. To gain insight into the cellular activities of anesthetics, we have isolated genes that, when overexpressed, render Saccharomyces cerevisiae resistant to the volatile anesthetic isoflurane. One of these genes, WAK3/TAT1, encodes a permease that transports amino acids including leucine and tryptophan, for which our wild-type strain is auxotrophic. This suggests that availability of amino acids may play a key role in anesthetic response. Multiple lines of evidence support this proposal: (i) Deletion or overexpression of permeases that transport leucine and/or tryptophan alters anesthetic response; (ii) prototrophic strains are anesthetic resistant; (iii) altered concentrations of leucine and tryptophan in the medium affect anesthetic response; and (iv) uptake of leucine and tryptophan is inhibited during anesthetic exposure. Not all amino acids are critical for this response since we find that overexpression of the lysine permease does not affect anesthetic sensitivity. These findings are consistent with models in which anesthetics have a physiologically important effect on availability of specific amino acids by altering function of their permeases. In addition, we show that there is a relationship between nutrient availability and ubiquitin metabolism in this response.

Anesthetic Effects on Mitochondrial ATP-sensitive K Channel

2001 ◽  
Vol 95 (6) ◽  
pp. 1435-1440 ◽  
Author(s):  
Shinji Kohro ◽  
Quinn H. Hogan ◽  
Yuri Nakae ◽  
Michiaki Yamakage ◽  
Zeljko J. Bosnjak
Keyword(s):  
Fluorescence Microscopy ◽  
Volatile Anesthetics ◽  
Cardioprotective Effect ◽  
K Channel ◽  
Myocardial Cells ◽  
Intravenous Anesthetics ◽  
Inhalational Anesthetics ◽  
Cardioprotective Effects ◽  
Cardiac Preconditioning ◽  
Dose Dependent

Background Volatile anesthetics show an ischemic preconditioning-like cardioprotective effect, whereas intravenous anesthetics have cardioprotective effects for ischemic-reperfusion injury. Although recent evidence suggests that mitochondrial adenosine triphosphate-regulated potassium (mitoK(ATP)) channels are important in cardiac preconditioning, the effect of anesthetics on mitoK(ATP) is unexplored. Therefore, the authors tested the hypothesis that anesthetics act on the mitoK(ATP) channel and mitochondrial flavoprotein oxidation. Methods Myocardial cells were isolated from adult guinea pigs. Endogenous mitochondrial flavoprotein fluorescence, an indicator of mitochondrial flavoprotein oxidation, was monitored with fluorescence microscopy while myocytes were exposed individually for 15 min to isoflurane, sevoflurane, propofol, and pentobarbital. The authors further investigated the effect of 5-hydroxydeanoate, a specific mitoK(ATP) channel antagonist, on isoflurane- and sevoflurane-induced flavoprotein oxidation. Additionally, the effects of propofol and pentobarbital on isoflurane-induced flavoprotein oxidation were measured. Results Isoflurane and sevoflurane induced dose-dependent increases in flavoprotein oxidation (isoflurane: R2 = 0.71, n = 50; sevoflurane: R2 = 0.86, n = 20). The fluorescence increase produced by both isoflurane and sevoflurane was eliminated by 5-hydroxydeanoate. Although propofol and pentobarbital showed no significant effects on flavoprotein oxidation, they both dose-dependently inhibited isoflurane-induced flavoprotein oxidation. Conclusions Inhalational anesthetics induce flavoprotein oxidation through opening of the mitoK(ATP) channel. This may be an important mechanism contributing to anesthetic-induced preconditioning. Cardioprotective effects of intravenous anesthetics may not be dependent on flavoprotein oxidation, but the administration of propofol or pentobarbital may potentially inhibit the cardioprotective effect of inhalational anesthetics.

Behavioral Effects of Volatile Anesthetics in Caenorhabditis elegans

1996 ◽  
Vol 85 (4) ◽  
pp. 901-912 ◽  
Author(s):  
Michael C. Crowder ◽  
Laynie D. Shebester ◽  
Tim Schedl
Keyword(s):  
Nervous System ◽  
Caenorhabditis Elegans ◽  
Time Course ◽  
Model Organism ◽  
Volatile Anesthetic ◽  
Volatile Anesthetics ◽  
Effective Concentration ◽  
Forward Genetics ◽  
C Elegans ◽  
Median Effective Concentration

Background The nematode Caenorhabditis elegans offers many advantages as a model organism for studying volatile anesthetic actions. It has a simple, well-understood nervous system; it allows the researcher to do forward genetics; and its genome will soon be completely sequenced. C. elegans is immobilized by volatile anesthetics only at high concentrations and with an unusually slow time course. Here other behavioral dysfunctions are considered as anesthetic endpoints in C. elegans. Methods The potency of halothane for disrupting eight different behaviors was determined by logistic regression of concentration and response data. Other volatile anesthetics were also tested for some behaviors. Established protocols were used for behavioral endpoints that, except for pharyngeal pumping, were set as complete disruption of the behavior. Time courses were measured for rapid behaviors. Recovery from exposure to 1 or 4 vol% halothane was determined for mating, chemotaxis, and gross movement. All experiments were performed at 20 to 22 degrees C. Results The median effective concentration values for halothane inhibition of mating (0.30 vol%-0.21 mM), chemotaxis (0.34 vol%-0.24 mM), and coordinated movement (0.32 vol% - 0.23 mM) were similar to the human minimum alveolar concentration (MAC; 0.21 mM). In contrast, halothane produced immobility with a median effective concentration of 3.65 vol% (2.6 mM). Other behaviors had intermediate sensitivities. Halothane's effects reached steady-state in 10 min for all behaviors tested except immobility, which required 2 h. Recovery was complete after exposure to 1 vol% halothane but was significantly reduced after exposure to immobilizing concentrations. Conclusions Volatile anesthetics selectively disrupt C. elegans behavior. The potency, time course, and recovery characteristics of halothane's effects on three behaviors are similar to its anesthetic properties in vertebrates. The affected nervous system molecules may express structural motifs similar to those on vertebrate anesthetic targets.

U46619, a thromboxane A2 agonist, inhibits KCa channel activity from pig coronary artery

1992 ◽  
Vol 262 (3) ◽  
pp. C708-C713 ◽  
Author(s):  
F. S. Scornik ◽  
L. Toro
Keyword(s):  
Smooth Muscle ◽  
Coronary Artery ◽  
Lipid Bilayers ◽  
Thromboxane A2 ◽  
Inhibitory Effect ◽  
Channel Activity ◽  
Open Probability ◽  
Control Value ◽  
Kca Channels ◽  
Internal Side

Thromboxane A2 (TxA2) is a potent vasoconstrictor derived from the metabolism of arachidonic acid. Because potassium channels are involved in the contraction of vascular smooth muscle, their blockade could contribute to the TxA2-induced contraction. To test this possibility, we studied the effect of the TxA2 stable analogue U46619 on calcium-activated potassium (KCa) channels from coronary artery reconstituted into lipid bilayers. Addition of U46619 (50-150 nM) to the external but not to the internal side of the channel decreased the channel open probability (Po) between 15 and 80% of the control value. The inhibitory effect of U46619 affected both the open and closed states of the channel and could be reversed by internal calcium. Thromboxane B2, the inactive hydrolysis derivative of TxA2, did not affect channel activity. SQ 29548, a TxA2 receptor antagonist, was able to prevent the inhibition by U46619. Furthermore, SQ 29548 added after U46619 could restore channel activity to near control values. These results suggest that TxA2 could be a regulatory factor of KCa channels from coronary smooth muscle and that this regulation could be related to its action as a vasoconstrictor.

Ryanodine receptor dysfunction in porcine stunned myocardium

1997 ◽  
Vol 273 (2) ◽  
pp. H796-H804 ◽  
Author(s):  
C. Valdivia ◽  
J. O. Hegge ◽  
R. D. Lasley ◽  
H. H. Valdivia ◽  
R. Mentzer
Keyword(s):  
Coronary Artery ◽  
Lipid Bilayers ◽  
Ryanodine Receptor ◽  
Myocardial Stunning ◽  
Single Channel ◽  
Stunned Myocardium ◽  
Wall Thickening ◽  
Planar Lipid Bilayers ◽  
Open Probability ◽  
Single Channel Recordings

We investigated the effects of myocardial stunning on the function of the two main Ca2+ transport proteins of the sarcoplasmic reticulum (SR), the Ca(2+)-adenosinetriphosphatase and the Ca(2+)-release channel or ryanodine receptor. Regional myocardial stunning was induced in open-chest pigs (n = 6) by a 10-min occlusion of the left anterior descending coronary artery (LAD) and 2 h reperfusion. SR vesicles isolated from the LAD-perfused region (stunned) and the normal left circumflex coronary artery (LC)-perfused region were used to assess the oxalate-supported 45Ca2+ uptake, [3H]ryanodine binding, and single-channel recordings of ryanodine-sensitive Ca(2+)-release channels in planar lipid bilayers. Myocardial stunning decreased LAD systolic wall thickening to 20% of preischemic values. The rate of SR 45Ca2+ uptake in the stunned LAD bed was reduced by 37% compared with that of the normal LC bed (P < 0.05). Stunning was also associated with a 38% reduction in the maximal density of high-affinity [3H]ryanodine binding sites (P < 0.05 vs. normal LC) but had no effect on the dissociation constant. The open probability of ryanodine-sensitive Ca(2+)-release channels determined by single channel recordings in planar lipid bilayers was 26 +/- 2% for control SR (n = 33 channels from 3 animals) and 14 +/- 2% for stunned SR (n = 21 channels; P < 0.05). This depressed activity of SR function observed in postischemic myocardium could be one of the mechanisms underlying myocardial stunning.

Stilbene disulfonate blockade of colonic secretory Cl- channels in planar lipid bilayers

1989 ◽  
Vol 256 (4) ◽  
pp. C902-C912 ◽  
Author(s):  
R. J. Bridges ◽  
R. T. Worrell ◽  
R. A. Frizzell ◽  
D. J. Benos
Keyword(s):  
Lipid Bilayers ◽  
Single Channel ◽  
Membrane Vesicles ◽  
Kinetic Scheme ◽  
Disulfonic Acid ◽  
Lipid Bilayer Membranes ◽  
Plasma Membrane Vesicles ◽  
Open Probability ◽  
Cl Channel ◽  
Cl Channels

We studied blockade by 4,4'-dinitrostilbene-2,2'-disulfonic acid (DNDS) of a secretory Cl- channel from colonic enterocyte plasma membrane vesicles incorporated into planar lipid bilayer membranes. Except for intermittent long-lived closed periods (100 ms to several min), the control channel open probability (Po) was greater than 90%. DNDS, added to the cis or vesicle-containing side, which corresponds to the outer membrane side of the channel, caused a dramatic increase in the number of current transitions from the open-to-closed state. DNDS caused a concentration-dependent decrease in Po with a maximum inhibition of 95 +/- 2.0% and a half-maximal inhibitory concentration of 3.3 +/- 1.4 microM. DNDS added to the trans side of the channel had no effect on either the single-channel conductance or kinetic behavior of the channel. Kinetic analysis revealed that DNDS blockade from the cis side could be explained by a linear, closed-open-blocked, kinetic scheme. The estimated DNDS block rate constants were kon = 3.2 X 10(7) M-1.s-1 and koff = 52 s-1, yielding an equilibrium dissociation constant (KD) of 2.1 +/- 0.38 microM, similar to the Ki for inhibition of Po. The effects of DNDS were fully reversible after perfusion of the cis compartment with DNDS-free solution. In contrast, the covalently reactive 4,4'-diisothiocyano-substituted stilbene disulfonate caused an irreversible blockade of the Cl- channel.

scholarly journals Interdomain Interactions within Ryanodine Receptors Regulate Ca2+ Spark Frequency in Skeletal Muscle

2001 ◽  
Vol 119 (1) ◽  
pp. 15-32 ◽  
Author(s):  
Alexander Shtifman ◽  
Christopher W. Ward ◽  
Takeshi Yamamoto ◽  
Jianli Wang ◽  
Beth Olbinski ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Lipid Bilayers ◽  
Laser Scanning ◽  
Muscle Fibers ◽  
Mammalian Skeletal Muscle ◽  
Open Probability ◽  
Release Channel ◽  
Pronounced Increase ◽  
Open Time ◽  
Interdomain Interactions

DP4 is a 36-residue synthetic peptide that corresponds to the Leu2442-Pro2477 region of RyR1 that contains the reported malignant hyperthermia (MH) mutation site. It has been proposed that DP4 disrupts the normal interdomain interactions that stabilize the closed state of the Ca2+ release channel (Yamamoto, T., R. El-Hayek, and N. Ikemoto. 2000. J. Biol. Chem. 275:11618–11625). We have investigated the effects of DP4 on local SR Ca2+ release events (Ca2+ sparks) in saponin-permeabilized frog skeletal muscle fibers using laser scanning confocal microscopy (line-scan mode, 2 ms/line), as well as the effects of DP4 on frog SR vesicles and frog single RyR Ca2+ release channels reconstituted in planar lipid bilayers. DP4 caused a significant increase in Ca2+ spark frequency in muscle fibers. However, the mean values of the amplitude, rise time, spatial half width, and temporal half duration of the Ca2+ sparks, as well as the distribution of these parameters, remained essentially unchanged in the presence of DP4. Thus, DP4 increased the opening rate, but not the open time of the RyR Ca2+ release channel(s) generating the sparks. DP4 also increased [3H]ryanodine binding to SR vesicles isolated from frog and mammalian skeletal muscle, and increased the open probability of frog RyR Ca2+ release channels reconstituted in bilayers, without changing the amplitude of the current through those channels. However, unlike in Ca2+ spark experiments, DP4 produced a pronounced increase in the open time of channels in bilayers. The same peptide with an Arg17 to Cys17 replacement (DP4mut), which corresponds to the Arg2458-to-Cys2458 mutation in MH, did not produce a significant effect on RyR activation in muscle fibers, bilayers, or SR vesicles. Mg2+ dependence experiments conducted with permeabilized muscle fibers indicate that DP4 preferentially binds to partially Mg2+-free RyR(s), thus promoting channel opening and production of Ca2+ sparks.

Sign in / Sign up

Export Citation Format

Share Document