Trifluoroacetic Acid Activates ATP-Sensitive K+ Channels in Rabbit Ventricular Myocytes

Han, Jin; Kim, Nari; Kim, Euiyong

doi:10.1006/bbrc.2001.5291

Cited by 10 publications

(13 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the light of the hypothesis that Aβ oligomers affect neuronal membranes and may interfere with cognitive functions by a membrane-dependent mechanism, this raises the question if effects reported earlier as Aβ oligomer-specific are augmented by or entirely attributable to the presence of residual HFIP. Furthermore, TFA can activate ATP-sensitive potassium channels at concentrations as low as 0.05 mM [33].…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Effect of Synthetic Aβ Peptide Oligomers and Fluorinated Solvents on Kv1.3 Channel Properties and Membrane Conductance

et al. 2012

View full text Add to dashboard Cite

The impact of synthetic amyloid β (1–42) (Aβ1–42) oligomers on biophysical properties of voltage-gated potassium channels Kv 1.3 and lipid bilayer membranes (BLMs) was quantified for protocols using hexafluoroisopropanol (HFIP) or sodium hydroxide (NaOH) as solvents prior to initiating the oligomer formation. Regardless of the solvent used Aβ1–42 samples contained oligomers that reacted with the conformation-specific antibodies A11 and OC and had similar size distributions as determined by dynamic light scattering. Patch-clamp recordings of the potassium currents showed that synthetic Aβ1–42 oligomers accelerate the activation and inactivation kinetics of Kv 1.3 current with no significant effect on current amplitude. In contrast to oligomeric samples, freshly prepared, presumably monomeric, Aβ1–42 solutions had no effect on Kv 1.3 channel properties. Aβ1–42 oligomers had no effect on the steady-state current (at −80 mV) recorded from Kv 1.3-expressing cells but increased the conductance of artificial BLMs in a dose-dependent fashion. Formation of amyloid channels, however, was not observed due to conditions of the experiments. To exclude the effects of HFIP (used to dissolve lyophilized Aβ1–42 peptide), and trifluoroacetic acid (TFA) (used during Aβ1–42 synthesis), we determined concentrations of these fluorinated compounds in the stock Aβ1–42 solutions by 19F NMR. After extensive evaporation, the concentration of HFIP in the 100× stock Aβ1–42 solutions was ∼1.7 μM. The concentration of residual TFA in the 70× stock Aβ1–42 solutions was ∼20 μM. Even at the stock concentrations neither HFIP nor TFA alone had any effect on potassium currents or BLMs. The Aβ1–42 oligomers prepared with HFIP as solvent, however, were more potent in the electrophysiological tests, suggesting that fluorinated compounds, such as HFIP or structurally-related inhalational anesthetics, may affect Aβ1–42 aggregation and potentially enhance ability of oligomers to modulate voltage-gated ion channels and biological membrane properties.

show abstract

Section: Resultsmentioning

confidence: 99%

“…Although extensively removed during purification and lyophilization, it is toxic to cells at high concentration. Moreover, TFA activates some types of potassium channels [33]. It is therefore critical to determine which effects are due to Aβ oligomers and which to HFIP or TFA.…”

Section: Introductionmentioning

confidence: 99%

Effect of Synthetic Aβ Peptide Oligomers and Fluorinated Solvents on Kv1.3 Channel Properties and Membrane Conductance

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Single ventricular myocytes were isolated by enzymatic dissociation method as reported previously [8, 9]. The rabbits were heparinized with 500U/kg heparin i.v., and anesthetized using 30 mg/kg pentobarbital.…”

Section: Methodsmentioning

confidence: 99%

“…The whole-cell voltage clamp method was used for recording membrane currents [9]. A small aliquot of the solution containing the isolated cells was put in an open perfusion chamber (1.5 ml) mounted on the stage of an inverted microscope (Olympus, 2 × 70-122, Japan).…”

Section: Methodsmentioning

confidence: 99%

Effects of diacetyl-liensinine on electrophysiology in rabbit ventricular myocytes

Cao

Wang

Ding

et al. 2017

BMC Pharmacol Toxicol

View full text Add to dashboard Cite

BackgroundDiacetyl-liensinine is a chemosynthetic derivative of liensinine, extracted from the seed embryo of Nelumbo nucifera Gaertn, in China. It has been found to have extensive anti- arrhythmic actions. The present study was designed to investigate the effects of diacetyl-liensinine on electro- physiology of myocytes.MethodsWe exposed rabbit ventricular myocytes to diacetyl-liensinine using standard whole-cell patch-clamp technique and measured the action potential, L-type calcium current (I Ca-L), delayed rectifier potassium current (I K), transient outward potassium current (I to) and inward rectifier potassium current (I K1).ResultsOur results showed that diacetyl-liensinine significantly prolonged action potential duration at 50 and 90% repolarization (APD50, APD90), at 10 and 30 μM, while shortened APD50 and APD90 at 100 μM. In addition, diacetyl-liensinine inhibited the ICa-L, IK, I to and IK1 in a concentration-dependent manner.ConclusionsThe results suggest that diacetyl-liensinine might be a potential anti-arrhythmic agent.

show abstract

“…It is thought to be responsible for the development of halothane-induced hepatitis and neurotoxicity (Gut et al, 1995; Ma et al, 1990) and may play a role in the cardioprotective effects of isofluorane (Han et al, 2001). …”

Section: Introductionmentioning

confidence: 99%

Trifluoroacetate is an allosteric modulator with selective actions at the glycine receptor

2012

View full text Add to dashboard Cite

Trifluoroacetic acid is a metabolite of the inhaled anesthetics halothane, desflurane and isoflurane as well as a major contaminant in HPLC-purified peptides. Ligand-gated ion channels, including cys-loop receptors such as the glycine receptor, have been the targets of peptide-based drug design and are considered to be likely candidates for mediating the effects of anesthetics in vivo, but the possible secondary contributions of contaminants and metabolites to these effects have not been studied. We used two-electrode voltage-clamp electrophysiology to test glycine, GABAA and 5-HT3 receptors expressed in Xenopus oocytes for their sensitivities to sodium trifluoroacetate. Trifluoroacetate (100 μM–3 mM) enhanced the currents elicited by low concentrations of glycine applied to α1 homomeric and α1β heteromeric glycine receptors, but it had no effects when co-applied with a maximally-effective glycine concentration. Trifluoroacetate had no effects on α1β2γ2S GABAA or 5-HT3A receptors at any GABA or serotonin concentration tested. The results demonstrate that trifluoroacetate acts as an allosteric modulator at the glycine receptor with greater specificity than other known modulators. These results have important implications for both the secondary effects of volatile anesthetics and the presence of contaminating trifluoroacetate in HPLC-purified peptides, which is potentially an important source of experimental variability or error that requires control.

show abstract

Trifluoroacetic Acid Activates ATP-Sensitive K+ Channels in Rabbit Ventricular Myocytes

Cited by 10 publications

References 18 publications

Effect of Synthetic Aβ Peptide Oligomers and Fluorinated Solvents on Kv1.3 Channel Properties and Membrane Conductance

Effect of Synthetic Aβ Peptide Oligomers and Fluorinated Solvents on Kv1.3 Channel Properties and Membrane Conductance

Effects of diacetyl-liensinine on electrophysiology in rabbit ventricular myocytes

Trifluoroacetate is an allosteric modulator with selective actions at the glycine receptor

Contact Info

Product

Resources

About