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Effects of noise on cochlear potentials and endolymph potassium concentration recorded with potassium-selective electrodes.

Guinea pig cochleas were exposed to either broad-band noise at intensities between 95 and 115 dBA or octave-band noise centered at 380 Hz or 4.2 kHz at intensities between 115 and 125 dB SPL. Cochlear microphonics (CM), summating potentials (SP) and action potentials (AP) were recorded from differential electrodes in the perilymphatic scalae between successive 20-min periods of noise exposure. The endocochlear potential (EP) and endolymph potassium concentration [Kendo+] were recorded continuously from scala media using double-barreled potassium-sensitive electrodes. It was found that the initial exposure to noise at 115 dBA produced considerable suppression of the CM and AP, while the EP and [Kendo+] were elevated above their normal values. When animals previously treated with kanamycin were subjected to the same level of noise exposure no systematic increase in either EP ro [Kendo+] was observed. After prolonged exposure to 380 Hz octave-band noise at 125 dB SPL, a slow decline of EP and [Kendo+] was observed. The relationships between the changes in EP, [Kendo+] and CM are discussed.

Animals↗

Glucose-insulin-potassium and reperfusion in acute myocardial infarction: rationale and design of the Glucose-Insulin-Potassium Study-2 (GIPS-2).

BACKGROUND: The combination of reperfusion therapy and high-dose glucose-insulin-potassium (GIK) infusion seems beneficial in acute myocardial infarction (MI). Current evidence, however, is not considered conclusive. STUDY DESIGN: The Glucose-Insulin-Potassium Study-2 (GIPS-2) will investigate whether GIK, in adjunction to reperfusion therapy, is beneficial in MI patients without signs of heart failure at admission. A total of at least 1044 patients with an acute MI treated with either thrombolysis or primary percutaneous coronary intervention will be randomized to an infusion of high-dose GIK or no infusion. The primary end point of the study is 30-day mortality. Secondary end points are mortality at 1 year, recurrence of MI, repeat intervention, and infarct size. IMPLICATIONS: If high-dose GIK significantly reduces mortality at 30 days in all patients, the adjunction of this treatment to reperfusion therapy may become part of standard regimen for patients with acute MI without heart failure.

Algorithms↗

One year outcomes after glucose-insulin-potassium in ST elevation myocardial infarction. The Glucose-insulin-potassium study II.

BACKGROUND: There are conflicting data concerning the effect of treatment with glucose-insulin-potassium (GIK) in ST segment elevation myocardial infarction (STEMI). Early studies showed beneficial effects of GIK, however, recent large sample size trials did not confirm this, or suggested only benefits in patients without heart failure. We aimed to evaluate long-term effects of GIK in patients with STEMI without signs of heart failure, all treated with reperfusion therapy. METHODS: From August 2003 to December 2004, 889 STEMI patients without signs of heart failure were randomized to standard care (N=445) or additional GIK infusion (N=444). Glucose-potassium (20% glucose with 80 mmol potassium/l) was infused at 2 ml/kg body weight per hour for 12 h through a peripheral line. Short-acting insulin was started according to admission glucose and adjusted based on hourly measured glucose. Clinical end points were of number of death, reinfarction and revascularization at 1 year. RESULTS: One year follow-up was available in 864 patients (97.2%), 432 in the GIK group and 432 in the control group. Mortality rate was 5.3% in GIK and 3.9% in control patients, p=0.33. Rates of reinfarction and revascularization 4.6% vs. 4.6% and 15.5% and 15.0%, in GIK vs. control patients. CONCLUSION: In patients with STEMI without signs of heart failure treated with reperfusion therapy, GIK therapy offers no clinical benefit at 1 year.

Aged↗

The KCNQ5 potassium channel from mouse: a broadly expressed M-current like potassium channel modulated by zinc, pH, and volume changes.

The KCNQ proteins compose a sub-group of the voltage-activated potassium channel family. The family consists of five members (KCNQ1 to 5--also named Kv7.1 to Kv7.5) encoded by single genes, which all give rise to proteins forming slowly activating potassium-selective ion channels. The physiological importance of the KCNQ channel family is emphasized by the fact that mutations in four of the five genes have been linked to human pathologies (KCNQ1 to 4). Here, we present the cloning and characterization of a novel KCNQ5 ortholog from mouse isolated by homology cloning from total mouse brain RNA (GenBank accession number: AY679158). The predicted protein is 95% identical to human KCNQ5. Upon expression in Xenopus oocytes, these proteins form voltage-dependent slowly activating channels with half-maximal activation at -21 mV. Our functional characterization revealed three novel modes of modulation: pH-dependent potentiation by Zn2+ (EC50 = 21.8 microM at pH 7.4), inhibition by acidification (IC50 = 0.75 microM; pKa = 6.1), and regulation by small changes in cell volume. Furthermore, the channels are activated by the anti-convulsant drug retigabine (EC50 = 2.0 microM) and inhibited by the M-current blockers linopiridine and XE-991. Finally, real-time RT-PCR was used to quantify the expression profile in a wide range of mouse tissues. These experiments revealed a relatively broad expression pattern in the nervous system but also expression in other tissues. Highest overall expression levels were observed in cortex and hippocampus. This study shows that murine KCNQ5 channels, in addition to sharing biophysical and pharmacological characteristics with the human ortholog, are tightly regulated by physiological stimuli such as changes in extracellular Zn2+, pH, and tonicity, thus adding to the complex regulation of these channels.

Animals↗

A single-file model for potassium transport in squid giant axon. Simulation of potassium currents at normal ionic concentrations.

A physical model for potassium transport in squid giant axon is proposed. The model is designed to explain the empirical data given by the Hodgkin-Huxley model and related experiments. It is assumed that K(+) moves across the axon membrane by single-file diffusion through narrow pores. In the model a pore has three negatively charged sites that can be occupied alternatively by K(+) or by a gating particle, GP(++), coming from the external surface. GP(++) is considered to be part of the membrane rather than a diffusible component of the surrounding solutions. A high activation barrier for GP(++) is supposed at the inner membrane border so that it cannot change over to the internal surface. Therefore potassium diffusion can be blocked by GP(++) penetrating into the pores. This mechanism controls the dynamic behaviour of the model. The time-dependent probabilities of the pore states are described by a system of differential equations. The rate constants in these equations depend on the ionic concentrations, the membrane voltage, and the electrostatic interaction between ions in a single pore. Detailed computational tests for normal composition of external and internal solutions show that the model agrees remarkably well with the stationary and dynamic behaviour of the Hodgkin-Huxley model. However, the hyperpolarization delay is not reproduced. A structural modification, concerning this delay and the way in which GP(++) is attached to the membrane, is proposed, and the qualitative behavior of the model at varied external and internal concentrations is discussed.

Animals↗

Anomalous potassium channel-gating rates as functions of calcium and potassium ion concentrations.

With near normal monovalent ionic concentrations, the rate of increase of the potassium conductance after a depolarizing voltage-clamp step is slowed when the external calcium concentration is increased. This trend in the rise-time with changes in calcium is reversed when the axointernal potassium concentration is reduced (150 mM) and the periaxonal concentration is increased (50 mM); that is, the rise-time decrease with increasing calcium concentration. Furthermore, the degree of sigmoidality of the K-conductance time-course always increase when the rise-times increase for a given test potential. In the case of calcium surface-charge screening, these effects may be caused by a shifted distribution of K-ions within the channels following the altered ion gradient, and by a consequent shift in the reciprocal electrostatic interactions between the ionic charges and channel-gate charges.

Animals↗

Glucose-insulin-potassium infusion inpatients treated with primary angioplasty for acute myocardial infarction: the glucose-insulin-potassium study: a randomized trial.

OBJECTIVES: In this study we considered the question of whether adjunction of glucose-insulin-potassium (GIK) infusion to primary coronary transluminal angioplasty (PTCA) is effective in patients with an acute myocardial infarction (MI). BACKGROUND: A combined treatment of early and sustained reperfusion of the infarct-related coronary artery and the metabolic modulation with GIK infusion has been proposed to protect the ischemic myocardium. METHODS: From April 1998 to September 2001, 940 patients with an acute MI and eligible for PTCA were randomly assigned, by open-label, to either a continuous GIK infusion for 8 to 12 h or no infusion. RESULTS: The 30-day mortality was 23 of 476 patients (4.8%) receiving GIK compared with 27 of 464 patients (5.8%) in the control group (relative risk [RR] 0.82, 95% confidence interval [CI] 0.46 to 1.46). In 856 patients (91.1%) without signs of heart failure (HF) (Killip class 1), 30-day mortality was 5 of 426 patients (1.2%) in the GIK group versus 18 of 430 patients (4.2%) in the control group (RR 0.28, 95% CI 0.1 to 0.75). In 84 patients (8.9%) with signs of HF (Killip class > or =2), 30-day mortality was 18 of 50 patients (36%) in the GIK group versus 9 of 34 patients (26.5%) in the control group (RR 1.44, 95% CI 0.65 to 3.22). CONCLUSIONS: Glucose-insulin-potassium infusion as adjunctive therapy to PTCA in acute MI did not result in a significant mortality reduction in all patients. In the subgroup of 856 patients without signs of HF, a significant reduction was seen. The effect of GIK infusion in patients with signs of HF (Killip class > or =2) at admission is uncertain.

Age Factors↗

Characterization of potassium and sodium-potassium alloy solutions containing metal anions and complexed cations by means of NMR and ESR techniques.

The influence of a complexing agent, kind of solvent and temperature on the stability and ionic composition of potassium and sodium-potassium alloy solutions containing metal anions and complexed cations as well as solvated electrons are discussed basing on the analysis of alkali metal NMR and ESR spectra. Surprisingly it seems that the stability of metal solutions in tetrahydrofuran at ambient temperature is inversely proportional to the durability of K+ complex in the case of five studied ligands. The most stable metal solutions were obtained using 15-crown-5. It was shown that the characteristic blue colour of metal solutions is not connected with the presence of solvated electrons but with metal anions.

Alloys↗

Syntheses and biological activities of potent potassium channel openers derived from (+/-)-2-oxo-1-pyridin-3-yl-cyclohexanecarbothioic acid methylamide: new potassium channel openers.

The syntheses and biological activities of (+/-)-2-(cyanomethylene)-1-pyridin-3-ylcyclohexanecarbothioic++ + acid methylamide (6) and trans-(+/-)-2-(cyanomethyl)-1-pyridin-3-ylcyclohexanecarbothioic acid methylamide (14) derived from (+/-)-2-oxo-1-pyridin-3-ylcyclohexanecarbothioic acid methylamide (4) are reported. Compounds were tested for antagonism of potassium-induced contraction of de-endothelialized rat aorta. The effects of modification of 6 and 14 on in vitro K(+)-channel opening activity are presented. These new series of potassium channel openers so derived are best exemplified by (+/-)-2-[2-(phenylsulfanyl)ethylidene]-1-pyridin-3-ylcyclohexan ecarbothioic acid methylamide (13d, RP 66266) and trans-(+/-)-2-[2-[(phenylsulfonyl)amino]ethyl]-1-pyridin-3- ylcyclohexanecarbothioic acid methylamide (25a, RP 66784), which have IC90 values of 3 and 0.3 nM, respectively. The potency of the most active compounds indicates a possible interaction at an extra binding site. The compounds described herein are potential antihypertensive and antianginal agents.

Animals↗

Mucosal irritant potential of a potassium-sparing diuretic and of wax-matrix potassium chloride.

To measure their relative upper gastrointestinal irritant potential, either 5 mg amiloride and 50 mg hydrochlorothiazide (twice daily) or 24 mEq wax-matrix potassium chloride (three times a day) were given to 30 normal subjects with no prior endoscopic abnormalities in the esophagus, stomach, or duodenum. All subjects received glycopyrrolate, 2 mg (3 times a day) to slow gastric emptying. Repeat endoscopy after 7 days of treatment with wax-matrix potassium chloride revealed that 10 of 15 (67%) of the subjects developed one or more gradable upper gastrointestinal lesions (esophageal ulcer, gastric ulcer, eight cases of one or more mucosal erosions, and four cases of hyperemia or edema of the esophagus, stomach, or duodenum). Four subjects (27%) taking amiloride/hydrochlorothiazide developed either mild hyperemia or edema, but there were no erosions or ulcers in this group.

Amiloride↗

Intracellular potassium. A determinant of the sodium-potassium pump rate.

Normal human red cells which have had their intracellular sodium (Na(c)) reduced have a diminished Na-K pump rate, but only if intracellular potassium (K(c)) is high. If most of the K(c) is replaced by tetramethylammonium or choline, both ouabain-sensitive Na efflux and K influx are significantly increased even with Na(c) below normal. Cells with reduced Na(c) and high K(c) have an unchanged Na efflux if external potassium (K(ext)) is removed. In contrast, low-Na, low-K cells have a large ouabain-sensitive Na efflux which shows a normal response to removal of K(ext). Neither low-K nor high-K cells have an altered ouabain-sensitive K efflux. Measurement at constant low Na(c) and varying K(c) shows the pump Na efflux to be an inverse function of K(c). Thus, in low-Na cells, K(c) appears to act as an inhibitor of the pump. Inhibition by high K(c) can be seen even when Na(c) is normal. The effects attributed to K(c) are distinguished experimentally from other variables such as cell volume, adenosine triphosphate concentration, effects of the replacement cations, and the method used to alter intracellular cation concentrations. A role is proposed for K(c), in cooperation with Na(c), in regulating the pump rate of normal human red cells.

Adenosine Triphosphate↗

Continuous intravascular monitoring of plasma potassium using potassium-selective electrode catheters.

A fast-responding, potassium-selective electrode catheter suitable for continuous intravascular monitoring is described. Traces illustrating its performance in human patients and anesthetized greyhounds are shown. There was no significant difference between off-line blood samples analysis (using an in vitro electrode) and results obtained with the in vivo electrode; mean absolute difference was 0.11 +/- 0.11 (SD) mM. The technique described is simple and reliable, and represents an advance on existing intermittent sampling methods for detailed monitoring of rapid changes in plasma potassium.

Animals↗

Opening of potassium channels in Escherichia coli membranes by thiol reagents and recovery of potassium tightness.

The retention of high potassium levels in Escherichia coli is not dependent on intact energy metabolism, since without the presence of a carbon source or in the presence of energy inhibitors significant K+ gradients can be maintained. In contrast, with 0.5 mM N-ethylmaleimide, K+ depletion is immediate and complete. As a final result, intracellular K+ is approximately three times more concentrated than the K+ in the medium. Increase of K+ in the medium is immediately followed by K+ uptake whereas in the unpoisoned state only an increase in the osmotic pressure of the medium would result in an increase of the K+ pool. The intracellular K+ undergoes continuous turnover in the poisoned cells whereas in intact cells turnover is strictly dependent on the presence of a metabolizable carbon source. After removal of the thiol reagent the cell recovers its capacity to concentrate potassium. The recovery process is inhibited by energy inhibitors or by incubation at low temperature but not by chloramphenicol. It is only slightly slowed down by carbon or sulfur starvation. The leak provoked by N-ethylmaleimide is similar in wild-type E. coli cells when a derepressed kdp uptake system working in the micromolar range of the K+ concentration is responsible for the intracellular pool of K+ and when, in a medium millimolar K+ concentration range, the trkA and trkD systems are predominant.

Biological Transport↗

Contractions induced by potassium-free solution and potassium relaxation in vascular smooth muscle of hypertensive and normotensive rats.

1. Vascular contractions induced by K(+)-free solution and relaxation responses following the return of K+ to the organ bath were studied in mesenteric arterial rings from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) with particular focus on the role of vascular adrenergic nerve-endings and endothelium. 2. In endothelium-denuded rings the omission of K+ from the incubation medium resulted in gradual contractions, the rate of which was slower in SHR than WKY. Nifedipine (1 microM) inhibited the contractions more effectively in SHR than WKY. 3. Adrenergic denervation in vitro with 6-hydroxydopamine reduced the contractions induced by the K(+)-free medium in endothelium-denuded rings. The remaining contractions after denervation were markedly greater in SHR than WKY. 4. The presence of intact vascular endothelium attenuated the K(+)-free contractions in both strains, the attenuation being smaller in SHR than WKY. NG-nitro-L-arginine methyl ester (L-NAME, 0.1 mM) and methylene blue (10 microM), but not indomethacin (10 microM), abolished the attenuating effect of endothelium on the K(+)-free contractions. L-Arginine (1 mM) reversed the effect of L-NAME in WKY but not in SHR. 5. The re-addition of K+ after full K(+)-free contractions dose-dependently relaxed the rings. The rate of this K(+)-induced relaxation was significantly slower in SHR than WKY at all K+ concentrations (0.1-5.9 mM) studied, whether the endothelium or functioning adrenergic nerve-endings were present or not. Ouabain (1 mM) totally inhibited the K+ relaxation in SHR but only partially in WKY.6. Vascular smooth muscle contractions induced by high concentrations of potassium were comparable between the strains. The EC50 for noradrenaline-induced contractions was lower in SHR than WKY, but the maximal forces did not differ significantly.7. In conclusion, the contractile response in K+-free solution more clearly differentiates vascular rings from SHR and WKY than the responses induced by the classical contractile agents noradrenaline and high concentrations of potassium. The depressant effect of the presence of intact endothelium on the K+-free contractions, which was smaller in SHR than WKY, is mediated via the endothelium-derived relaxing factor. Neurotransmitter release from vascular adrenergic nerve-endings participates less in the K+-free contractile response in SHR than WKY. Moreover, the contractile response is more dependent on calcium entry through nifedipine-sensitive calcium channels in SHR than WKY. The greater K+-free contractions of denervated endothelium-denuded rings and the reduced K+ relaxation rate in SHR when compared to WKY suggest increased cell membrane permeability and decreased activity of vascular Na+, K+-ATPase, respectively, in this type of genetic hypertension.

Analysis of Variance↗

Stimulation and inhibition by ATP and orthophosphate of the potassium-potassium exchange in resealed red cell ghosts.

The potassium:potassium (K-K) exchange through the sodium pump has been measured as the ouabain-sensitive 86Rb uptake by Na-free ghosts resealed to contain various concentrations of ATP, orthophosphate and K. The exchange is activated by increasing either internal or external K+ (Rb+) ion concentration. The activation curves can be described by simple Michaelis kinetics as: exchange = Vmax [K]/(Kapp + [K]). Increasing ATP concentration increases the apparent affinity for external K ions but decreases the apparent affinity for internal K (Ki+). Increasing [ATP] from 1 microM to 1 mM typically increases the Kapp for Ki+ from less than 1 mM to about 30 mM. Increasing ATP first activates the exchange but, after an optimal concentration is reached, further increase of ATP inhibits. The value of ATP concentration which gives the maximum flux depends on the internal and external K+ concentrations. The higher [Ki], the greater the optimal ATP concentration. Increasing external K (Rb) decreases the optimal ATP concentration. Increasing the concentration of orthophosphate (Pi) activates the exchange at high ATP but inhibits at low ATP concentration. A concentration of Pi which stimulates the exchange at high external K (Rb) can inhibit at low external K (Rb). These findings are in agreement with a consecutive or ping-pong model of the K-K exchange. We suggest that previous experiments have not shown the inhibitory effects of ATP and Pi because of the particular range of concentrations investigated.

Adenosine Triphosphate↗

Voltage-activated cation permeability in high-potassium but not low-potassium red blood cells.

We have recently reported that voltage-activated fluxes of Na, K, and Ca occur in human red blood cells [J.A. Halperin, C. Brugnara, M. Tosteson, T. Van Ha, and D. C. Tosteson. Am. J. Physiol. 257 (Cell Physiol. 26): C986-C996, 1989]. The cation permeability increases progressively as the membrane potential becomes more inside positive above +20 mV. In this paper we show that this effect also occurs in high-potassium (HK), but not in low-potassium (LK), sheep and dog red blood cells. This result suggests that the voltage-activated cation transport pathway is not the result of nonspecific dielectric breakdown of the lipid bilayer but, rather, relates to some membrane component, presumably a protein, that is expressed in HK human and sheep but not in LK sheep and dog red blood cells.

Animals↗

Influence of potassium ions and osmolality on the resting membrane potential of rabbit ventricular papillary muscle with estimation of the activity and the activity coefficient of internal potassium.

Resting membrane potentials of rabbit right ventricular papillary muscles were measured in modified Tyrode's solutions that were isotonic (1.0 X T), hypertonic (1.58 X T), or hypotonic (0.76 X T) at eight different concentrations of external potassium, [K]o, ranging from 0.78 to 100 mM. The amount of hyperpolarization produced by exposure to the hypertonic solutions was relatively constant with an average of 4.6 mv at all levels of [K]o except 0.78 and 1.56 mM. This potential change is much less than the 10.6 mv which would be predicted if the papillary muscles behaved as nearly perfect osmometers and the activity coefficient of intracellular potassium (K) remained constant. The amount of depolarization produced by exposure to the 0.76 X T hypotonic solutions averaged 6.8 mv at all levels of [K]o except 0.78 mM; this value is close to the predicted value of 6.9 mv. Variations in the activity and the activity coefficient of intracellular K were introduced to explain these discrepancies. We estimated that the activity of intracellular K in 1.58 X T hypertonic solution was increased 15-23% compared with that in isotonic solution. This change is much less than the 58% that would be predicted if the papillary muscle behaved as a nearly perfect osmometer. We also estimated that the activity of intracellular K in 0.76 X T hypotonic solution fell 22-26%, which is very close to the predicted value of 24%. The activity coefficient of intracellular K appeared to fall in 1.58 X T hypertonic solution to about 0.76 of its value in isotonic solution. This decline in the estimated activity coefficient of intracellular K could not be attributed to an increase in Coulombic attractive and repulsive forces as predicted by the Debye-Hückel equation for a univalent electrolyte.

Animals↗

Comparison of potassium ISFETs with the Radiometer KNA1 and the Corning 902 ion selective electrode analysers for whole blood potassium ion estimation.

Evaluation of the performance of potassium ion sensitive field effect transistors (K+ ISFETs), developed by Thorn EMI in a form suitable for mass production and for incorporation in 'near the patient' analysers, showed only very small constant and proportional biases against the Radiometer KNA1 and the Corning 902 for whole blood potassium ion estimation. Between batch imprecision tests with whole blood showed the K+ ISFET was comparable in performance to the Corning 902 but inferior to the Radiometer KNA1. The evaluation demonstrated that ISFET manufacturing technology has now reached a stage of development at which ISFETs should be considered seriously for use in clinical chemical analysers.

Calibration↗