Potential Duration Research Articles

Seed Priming Improves the Germination Traits of Tall Fescue (Festuca arundinacea)

A couple of experiments were carried out to investigate the effects of osmopriming and hydropriming treatments on the germination indexes and seed vigor of Tall fescue (Festuca arundinacea). In the first experiment, fulfilled based on randomized complete block designed with four replicates, the effect of polyethyleneglycol 6000 solution with five osmotic potentials (-8, -10, -12, -14 and -16 bar), two temperatures (15 and 25oC) and four time intervals (12, 24, 36 and 48 hours) was analized. The second experiment was fulfilled by using distilled water at two temperatures (15 and 25oC) and four time intervals (12, 24, 36 and 48 hours) with four replicates on the above mentioned data. Then, based on the maximum germination rate and vigor indexes, the optimal treatment composition was determined for osmopriming and hydropriming solutions in regard to the osmotic potential, temperature and priming duration. In osmopriming experiment, treatment composition of 12 hours at 15oC and -8 bar had the most significant effect on the percent and speed of germination, length of radicle, coleoptile and seedling, as well as vigor indexes in Tall fescue. For hydropriming, the effect analyzed in the same condition as osmopriming, was observed in the majority of evaluated traits; treatment composition of 12 hours prime and 15oC had the maximum numerical value in comparison to control and other treatments. Finally, it is inferred that favorable effects of osmo- and hydropriming at 15oC temperature are more significant in comparison with the control group (none prime seeds).

Drug evaluation in cardiomyocytes derived from human induced pluripotent stem cells carrying a long QT syndrome type 2 mutation

AimsCongenital long QT syndromes (LQTSs) are associated with prolonged ventricular repolarization and sudden cardiac death. Limitations to existing clinical therapeutic management strategies prompted us to develop a novel human in vitro drug-evaluation system for LQTS type 2 (LQT2) that will complement the existing in vitro and in vivo models.Methods and resultsSkin fibroblasts from a patient with a KCNH2 G1681A mutation (encodes IKr potassium ion channel) were reprogrammed to human induced pluripotent stem cells (hiPSCs), which were subsequently differentiated to functional cardiomyocytes. Relative to controls (including the patient's mother), multi-electrode array and patch-clamp electrophysiology of LQT2–hiPSC cardiomyocytes showed prolonged field/action potential duration. When LQT2–hiPSC cardiomyocytes were exposed to E4031 (an IKr blocker), arrhythmias developed and these presented as early after depolarizations (EADs) in the action potentials. In contrast to control cardiomyocytes, LQT2–hiPSC cardiomyocytes also developed EADs when challenged with the clinically used stressor, isoprenaline. This effect was reversed by β-blockers, propranolol, and nadolol, the latter being used for the patient's therapy. Treatment of cardiomyocytes with experimental potassium channel enhancers, nicorandil and PD118057, caused action potential shortening and in some cases could abolish EADs. Notably, combined treatment with isoprenaline (enhancers/isoprenaline) caused EADs, but this effect was reversed by nadolol.ConclusionsFindings from this paper demonstrate that patient LQT2–hiPSC cardiomyocytes respond appropriately to clinically relevant pharmacology and will be a valuable human in vitro model for testing experimental drug combinations.

T-wave alternans simulation by change in action potential time duration

number and absolute value of maxima and minima were assessed for every map. Results: Only bipolar maps (bp) were recorded in the healthy control group; mp were found in 55% (12) of the heart failure patients (mp with multiple minima, multiple maxima, or both multiple minima and maxima). All patients with mp IQRST had also mp IPST, 67% mp IPQRS, 33% mp IQ40, 17% mp IQRS, 67% mp ISTT, and 50% mp IST maps. Significant differences were noticed in maxima and minima in heart failure patients compared with healthy controls (IQ40 maxima: 14 ± 9 mV.ms in heart failure patients vs 16 ± 3.8 mV.ms in healthy controls, P = .014). We found significant different IPST minima and IST maxima in heart failure patients with mp IQRST maps compared with those with bp IQRST maps. IQRST maxima (119 ± 48 mV.ms vs 68 ± 17 mV.ms, P = .0026) and minima (−72 ± 28 mV.ms vs −40 ± 10 mV.ms, P = .0057) were also significantly different in patients with mp IQRST maps compared with those with bp IQRST maps. IQ40 maxima (7.5 ± 3.4 mV.ms vs 17 ± 7.8 mV.ms, P = .00054) and minima (−5 ± 2.44 vs −19 ± 11.7 mV.ms, P = .006) and IQRS minima (−26 ± 11 mV.ms vs −47 ± 28 mV.ms, P = .038) were significantly different in heart failure patients with mp IQ40 vs IQRS maps compared with those with bp maps. Ventricular arrhythmia appeared in 18% (4) of the heart failure patients. Patients with mp IST maps were more likely to die suddenly than patients with mp IQRST maps (odds ratio [OR], 2.5; 95% confidence interval [CI], 0.125-49.86), mp IPST maps (OR, 3; 95 %CI, 0.153-58.74), and mp IPQRS maps (OR, 2; 95% CI, 0.097-41). Conclusion: Postinfarction heart failure is associated with an increased prevalence of multipolar maps and causes significant changes of maxima and minima. Multipolar isointegral ST maps are better predictors of sudden cardiac death compared with multipolar IQRST, IPST, or IPQRS maps.

TOT does not affect the urethral sphincter innervation: a pilot study

To exclude a neuromuscular denervation damage due to prosthetic mini-invasive surgery using transobturator tape (TOT) by pre and postoperative electromyography (EMG) of the striated urethral sphincter. Seventeen women with SUI were enrolled by urogynecologic and urodynamic examination. Each of them underwent EMG of striated urethral sphincter performed by 25-mm concentric needle that was put in as far as 5 mm inside internal urethral sphincter. Amplitude and duration of EMG potentials were measured during caught, maximal contraction, and at rest. Four months after TOT treatment women underwent EMG. The mean amplitude of EMG potentials does not show significant statistical differences between pre- and post-TOT (P=NS). The duration of potentials, instead, changed between pre and posttreatment only during the maximal contraction test (P ≤ 0.05). TOT prosthesis surgery, avoiding denervation and devascularization of pelvic structures does not produce damage of the urethral sphincter.

ACCOUNTING FOR LEVEE OVERTOPPING DURATION: A TEST WITH HURRICANE KATRINA CONDITIONS

Overtopping of earthen levees can result in lee side erosion, levee failure and severe flooding consequences. Erosion takes time and early design guidance did not account for overtopping duration. The potential overtopping durations associated with hurricanes depends on the time histories of the surges and waves and are usually shorter than for riverine or coastal flooding by other storm types. With significant advancements in hurricane-induced storm surge modeling, it is appropriate to improve the levee erosion response characteristics. This paper presents the results of a blind-folded comparison of a method developed by Dean, et al (2010) to two levee locations in the New Orleans area. The levees failed in one area where the waves were larger than the second area where the levees performed well. The method applied accounts for surge and wave time histories, levee geometry and grass cover quality. Results are consistent with failure at the location of higher wave heights; however, the method also predicts failure at the location where levee function was retained. At the latter location, for good quality grass cover and a wave period of 4 s, a required levee crest elevation of 5.9 m is determined compared to an actual elevation of 5.8 m. For poor grass quality and a wave period of 8 s, the method indicates a required crest elevation of 7.4 m. The method can be applied to optimize levee design, for example, through investigating the trade offs between crest elevation and levee side slopes.

HLA-B27 and an Electrocardiographic Peculiarity

Introduction: An increased cardiovascular mortality has been described in patients with spondyloarthropathies due to HLA-B27. Numerous cardiovascular afflictions are currently known to be associated with HLA-B27. These include aortic root dilation, aortic regurgitation, mitral regurgitation, myocarditis, heart failure, pericarditis, pericardial effusion, atrioventricular conduction block and more recently, the presence of J-waves. Materials and methods: 48 HLA-B27 positive patients (23 men and 25 women) were included in this observational study. A 12-lead electrocardiogram and a signal-averaged electrocardiogram was recorded in every patient in order to detect any possible J-waves and ventricular late potentials respectively. Results: 27 out of these 48 patients demonstrated a visible J-wave in the inferolateral leads. It was revealed that there is a likelihood ratio of 11.386 (p=0.00074) to demonstrate a visible J-wave if the duration of low-amplitude signals is less than 30 ms. Conclusion: HLA-B27 positive patients has a high incidence of inferolateral cardiac J-waves. There is a high probability of demonstrating such a J-wave on the 12-lead electrocardiogram if the duration of ventricular late potentials is less than 30 ms. The possible mechanisms of this electrocardiographic paradox is discussed.

FUNCTIONAL AND MORPHOLOGICAL EFFECTS OF INDIRECT GRADUAL ELONGATION OF PERIPHERAL NERVE: ELECTROPHYSIOLOGICAL AND MORPHOLOGICAL CHANGES AT DIFFERENT ELONGATION RATES

We investigated the neuropathy induced by leg lengthening histological evaluation using teased nerve fiber specimens and electrophysiological evaluation. Indirect elongation of the sciatic nerve associated with leg lengthening was performed at 1 and 3 mm/day over 30 mm in rats. Electrophysiological evaluation was performed immediately and 60 days after the end of elongation, teased nerve fiber specimens were prepared, and the mean axonal diameter was calculated. The electrophysiological results were more wrong, and the recovery was poorer, in the 3-mm than in the 1-mm group. In the 1-mm group, the nerve conduction velocity (NCV) and the duration of the compound nerve action potential (C-NAP) recovered to a level close to the intact side, but the decrease in the amplitude of the C-NAP persisted. In the teased fiber study, while paranodal demyelination was observed in both groups immediately after elongation, demyelination was decreased in the 1-mm group indicationg recovery compared to the 3-mm group. Paranodal demyelination caused by indirect nerve elongation is considered to have induced electrophysiological disorders. Electrophysiological and morphological damages appeared to be more severe according to elongation speed. The nerve disorder were remained even at 1 mm per day in 60 days.

A global synergy of ions and voltage?

Membrane voltage and intracellular ion concentrations change under various cell states. Changes of both membrane potential and ion concentration can be sensed by the same elements in cell membranes. The calcium-activated potassium channels are a typical example. In hippocampal neurons, action potential waveforms are adapted to repetitive electrical inputs based on calcium-dependent repolarization. This may occur quickly or slowly. In the fast process, the duration of a single action potential becomes shorter. In the slow process, spike frequency and patterns are changed. The fast process is mainly achieved by activation of a class of Kv channel, a BK-type calcium-activated potassium channel. Its activities are regulated by both increase of intracellular calcium and depolarization. In fact, the BK channel has a voltage sensor domain and a cytoplasmic calcium-sensing domain. BK channels are often co-localized with voltage-gated calcium channels and can sense local and rapid calcium increase following opening of a single voltage-gated calcium channel during an action potential. The slower process of modification of neuronal firing depends on another class of potassium channel, the small conductance calcium-activated potassium channel (the SK channel), which binds calmodulin on the intracellular side. In contrast with the BK channel, the SK channel lacks intrinsic voltage dependence. Synergy between membrane voltage change and ions is not restricted to neurons and myocytes. In phagocytes such as the neutrophil or macrophage, reactive oxygen species are produced by the actions of NADPH oxidase. This activity induces remarkable depolarization since superoxide anions are transferred to the external space leaving protons inside. Thus both depolarization and intracellular acidification occur by the oxidase's activity. The voltage-gated proton (Hv) channel serves as an ideal player for cancelling both outcomes of the oxidase activity. The Hv channel is activated by both depolarization and intracellular acidification. Voltage dependence of steady-state open probability measured as the conductance–voltage (G–V) curve is shifted dependent on both intracellular and extracellular pH values. Recently, the molecular correlate of the Hv channel was identified. Knockout mice for the Hv channel exhibit reduced production of superoxide anions in neutrophils, consistent with the view that the Hv channel plays a role in promoting NADPH oxidase activity. More roles of the Hv channel in other cell types are also emerging. A study of knockout mice for the Hv channel led to the identification of unexpected roles in the signals of antibody production in B-lymphocytes. Another surprise was its presence and potential role in human sperm. Many ion channel species are expressed in sperm, but how ion channels contribute to sperm physiology, such as motility, has remained unknown. Patch clamping of sperm has now brought about a revolution in this field. This series of reviews covers three ion channel topics that explore the sites of synergy between voltage and ions. Jianmin Cui reviews recent findings of the structure–function relationship of the BK-type calcium-activated potassium channel (Cui, 2010). The interaction between S4, a key transmembrane segment of the voltage sensor domain, and the cytoplasmic metal ion-binding sites is one focus and the recently resolved X-ray structure of the cytoplasmic domain for calcium sensing is also discussed. Demaurex & Chemaly (2010) review the historical background of the Hv channel in leukocytes and recent molecular studies. Finally, Lishko & Kirichok (2010) review the recent discovery of the Hv channel in human sperm and its functional coupling with the CatSper channel, another class of voltage sensor containing channel that operates as an alkalization-activated calcium channel.

Realistic cardiac electrophysiology modelling: are we just a heartbeat away?

Realistic cardiac electrophysiology modelling: are we just a heartbeat away?

Low Prevalence of Chronic Beryllium Disease Among Workers at a Nuclear Weapons Research and Development Facility

To study the prevalence of beryllium sensitization (BeS) and chronic beryllium disease (CBD) in a cohort of workers from a nuclear weapons research and development facility. We evaluated 50 workers with BeS with medical and occupational histories, physical examination, chest imaging with high-resolution computed tomography (N = 49), and pulmonary function testing. Forty of these workers also underwent bronchoscopy for bronchoalveolar lavage and transbronchial biopsies. The mean duration of employment at the facility was 18 years and the mean latency (from first possible exposure) to time of evaluation was 32 years. Five of the workers had CBD at the time of evaluation (based on histology or high-resolution computed tomography); three others had evidence of probable CBD. These workers with BeS, characterized by a long duration of potential Be exposure and a long latency, had a low prevalence of CBD.

The quest for an anti-arrhythmic drug against atrial fibrillation that combines efficacy with safety

This editorial refers to ‘The combined ion channel blocker AZD1305 attenuates late Na current and I Kr-induced action potential prolongation and repolarization instability’ B. Andersson et al ., on page 1003 There is a long history at AstraZeneca to succeed in developing an anti-arrhythmic agent that can safely and effectively restore and maintain sinus rhythm in atrial fibrillation (AF) patients.1–7 For that purpose, the company developed agents that shared the property to suppress the rapid component of the delayed rectifier current ( I Kr, Table 1). These drugs prolong repolarization quantified as QT times in vivo or as duration of the action potential (APD) in vitro and are classified as Class III anti-arrhythmics. This strategy is effective against AF, but carries the risk of ventricular pro-arrhythmia, meaning that the drugs may be unsafe. With time proceeding, I Kr block was accompanied in the properties of the drug by inhibiting effects on other ion currents, especially the L-type calcium current ( I CaL) and both the peak and the late sodium current ( I Na and I Na late, respectively). This combined ion channel block, by preventing the occurrence of early afterdepolarizations (EADs) and spatial dispersion of repolarization, would lead to protection against Torsade de Pointes (TdP) pro-arrhythmia, while maintaining the high efficacy against …

Bioelectrical activity in the heart of the lugworm Arenicola marina

Standard microelectrode technique was used to study electrical activity of the isolated heart of the polychaete annelid, Arenicola marina. Typical pacemaker activity with slow diastolic depolarization was observed in all recordings. The average maximum diastolic potential (-58.4 +/- 3.2 mV), the average amplitude of the action potential (28.7 +/- 4.7 mV) and the average total duration of the action potential (2,434 +/- 430 ms) were determined. There has been no gradient of automaticity observed in our studies, which suggests that all regions of the Arenicola heart could possess pacemaker functions. Acetylcholine (ACh) produced a concentration dependent (5 x 10(-8)-5 x 10(-5) M) increase of the beating rate via increase in the rate of the diastolic depolarization. ACh (5 x 10(-5) M) increased beating rate by 2.5-fold compared to the control rate. A stronger action of ACh resulted in depolarization, block of action potential generation and contracture of the heart. The non-hydrolysable ACh analog carbacholine (10(-8)-10(-6) M) produced similar effects. All effects of ACh and carbacholine were abolished by 5 x 10(-6) M atropine. D-Tubocurarine (5 x 10(-5) M) did not significantly alter effects of ACh or carbacholine. Epinephrine (10(-8)-10(-6) M) caused the slowing of pacemaker activity and marked decrease of action potential duration. 10(-6) M epinephrine produced complete cardiac arrest. The effects of epinephrine were not significantly altered by the beta-blocker propranolol (5 x 10(-6) M). The beta-agonist isoproterenol (10(-7)-10(-5) M) and the alpha-agonist xylometazoline (10(-6)-10(-5) M) did not produce significant effects. Thus, cholinergic effects in the Arenicola heart are likely to be mediated via muscarinic receptors, while the nature of adrenergic effects needs further investigation.

Effects of Acetaldehyde on Membrane Potentials and Ionic Currents in Single Cardiac Myocytes

The effect of acetaldehyde on membrane potential and ionic currents in guinea-pig single ventricular myocytes using whole-cell voltage-clamp methods was studied. Exposure to acetaldehde at concentrations between 0.3 and 1 mM increased the overshoot and plateau phase of action potentials in a dose-dependent and reversible manner. The duration of action potentials measured at 90% repolarization was prolonged by acetaldehyde. Potassium currents were not affected by acetaldehyde at concentrations up to 1 mM. Voltage-dependent Ca2+ current (ICa) increased significantly when 0.3 mM acetaldehyde was applied. The effect of acetaldehyde on membrane potential and ionic currents was not modified by the β-adrenergic receptor blocker propranolol. Application of isoproterenol increased ICa in the presence of acetaldehyde. The results suggest that the increased ICa produced by acetaldehyde was not mediated through β1-adrenergic receptor or intracellular adenylate cyclase stimulation.

The Roles of ID, IA and IK in the Electrophysiological Functions of Small-Diameter Rat Trigeminal Ganglion Neurons

The Kv currents are divided into three different K+ currents, such as slow inactivating transient K+ current (I(D)), fast inactivating transient K+ current (I(A)) and dominant sustained K+ current (I(K)), in small-diameter rat trigeminal ganglion (TG) neurons. The concentration of alpha-DTX (an I(D) blocker) to evoke the maximal inhibition of I(A) was 0.1 microM, and this concentration caused a 20 % inhibition of I(A) and increased the number of action potentials. Irrespective of the presence of 0.1 microM alpha-DTX, the application of 0.5 mM 4-AP (an IA blocker) caused a 51 % inhibition of I(A) and increased the number of action potentials. The responses were associated with the decreases in the resting membrane potential (RMP) and duration of depolarization phase of action potential (DDP). The application of 2 mM tetraethylammonium (TEA, an I(K) blocker) produced a 55 % inhibition of I(K). Irrespective of the presence of both I(D) and I(A) blockers, the I(K) was the predominant K+ current. The prolongation of duration of action potential was usually observed following TEA treatment, suggesting that I(A) and I(K) had independent effects regulating the intrinsic firing properties of the action potential number and timing, respectively. Furthermore, the response characteristics of action potentials in the presence of both 4-AP and TEA resemble those of TG neurons in rats following chronic constriction nerve injury of the infraorbital nerve as well as after inferior alveolar nerve section. Thus, reducing effects of both I(A) and I(K) may be useful to investigate the mechanism of allodynia.

Clobutinol Delays Ventricular Repolarization in the Guinea Pig Heart: Comparison With Cardiac Effects of hERG K+ Channel Inhibitor E-4031

Clobutinol has been clinically reported to induce long QT syndrome. To clarify its cardiac electrophysiological properties, we compared effects of clobutinol on the isolated myocardium and anesthetized guinea pig heart with those of a hERG K channel blocker, E-4031. In isolated guinea pig ventricular tissues, clobutinol (3 microM) as well as E-4031 (10-100 nM) prolonged the action potential duration without affecting maximum upstroke velocity, but no further prolongation was observed after application of 30 microM clobutinol. In anesthetized closed-chest guinea pigs, clobutinol (1 and 10 mg/kg, intravenously) and E-4031 (0.01 and 1 mg/kg, intravenously) prolonged the QT interval and duration of the monophasic action potential (MAP) in a dose-dependent manner and at the same time increased the beat-to-beat variability of the MAP duration and reversed use-dependent prolongation of the MAP duration and triangulation of the MAP configuration. These results suggest that clobutinol delayed the ventricular repolarization and increased the proarrhythmic parameters linked to the hERG K channel inhibitor-induced torsade de pointes arrhythmias.

The electrophysiological and hemodynamical effects of pyruvate on diabetic and control rat hearts

Background Pyruvate, as an end-product of glycolysis, might influence the electrophysiological parameters of the heart by several mechanisms: Pyruvate enhances the phosphorylating potency of the cytosol; it can facilitate the reduction of inorganic phosphate and finally can influence the cytoplasamatic redox state by decreasing the H+ concentration. According to the literature, pyruvate enhances the amplitude of the action potential (APA) and also reduces the duration of the action potential (APD); hereby, it might be used to enhance the contractility in case of heart failure. Our aim was to determine the electrophysiological and hemodynamical effects of pyruvate on diabetic and control rat hearts.

Enhanced efficacy with MgSO4 due to an additive, alternative, or dual mode of action?

Pharmacological conversion of atrial fibrillation–atrial flutter (AF–AFl) is still an important therapeutic modality in daily patient care. Frequently used drugs are the class III anti-arrhythmics dofetilide, sotalol, and ibutilide. By blocking (specific) potassium currents, they will prolong the duration of the action potential (APD) providing less space for re-entry to manoeuvre. Their effectiveness is still not optimal and is also hampered by their pro-arrhythmic risk due to dose-dependent lengthening of the (ventricular) repolarization times. Their use is therefore restricted, including hospitalizations when therapy is started, as was the case in this single site (Hartford Hospital) retrospective investigation (2000–08) about the effectiveness of dofetilide to acutely convert AF–AFl.1 To protect their patients for dofetilide-induced torsade de pointes (TdP) arrhythmias, some ( n = 50) from the 160 eligible patients with AF–AFl received adjunctive magnesium sulfate (Mg). The evaluation demonstrated that a single or repeated bolus of Mg (mean ± 3 g MgSO4) did not only protect for drug-induced adverse effects (0/50 vs. 1/110 TdP occurrences), but also improved the efficacy of dofetilide to suppress/prevent AF–AFl: 38% without vs. 50% with Mg, P < 0.05. This important improvement with this combination (doubling of the odds), which was recently also shown for ibutilide and Mg by … *Corresponding author. Tel: +31 30 2538900, Fax: +31 30 2539036, Email: m.a.vos{at}umcutrecht.nl

From in vivo plasma composition to in vitro cardiac electrophysiology and in silico virtual heart: the extracellular calcium enigma

In spite of its potential impact on simulation results, the problem of setting the appropriate Ca(2+) concentration ([Ca(2+)](o)) in computational cardiac models has not yet been properly considered. Usually [Ca(2+)](o) values are derived from in vitro electrophysiology. Unfortunately, [Ca(2+)](o) in the experiments is set significantly far (1.8 or 2 mM) from the physiological [Ca(2+)] in blood (1.0-1.3 mM). We analysed the inconsistency of [Ca(2+)](o) among in vivo, in vitro and in silico studies and the dependence of cardiac action potential (AP) duration (APD) on [Ca(2+)](o). Laboratory measurements confirmed the difference between standard extracellular solutions and normal blood [Ca(2+)]. Experimental data on human atrial cardiomyocytes confirmed literature data, demonstrating an inverse relationship between APD and [Ca(2+)](o). Sensitivity analysis of APD on [Ca(2+)](o) for five of the most used cardiac cell models was performed. Most of the models responded with AP prolongation to increases in [Ca(2+)](o), i.e. opposite to the AP shortening observed in vitro and in vivo. Modifications to the Ten Tusscher-Panfilov model were implemented to demonstrate that qualitative consistency among in vivo, in vitro and in silico studies can be achieved. The Courtemanche atrial model was used to test the effect of changing [Ca(2+)](o) on quantitative predictions about the effect of K(+) current blockade. The present analysis suggests that (i) [Ca(2+)](o) in cardiac AP models should be changed from 1.8 to 2 mM to approximately 1.15 mM in order to reproduce in vivo conditions, (ii) the sensitivity to [Ca(2+)](o) of ventricular AP models should be improved in order to simulate real conditions, (iii) modifications to the formulation of Ca(2+)-dependent I(CaL) inactivation can make models more suitable to analyse AP when [Ca(2+)](o) is set to lower physiological values, and (iv) it could be misleading to use non-physiological high [Ca(2+)](o) when the quantitative analysis of in vivo pathophysiological mechanisms is the ultimate aim of simulation.

The temperature-induced changes in membrane potential.

Excitability and response properties of a neuron may vary in different environmental conditions of temperature. Increase/decrease of membrane potential has been observed under increase/decrease of temperature in the external side of membrane compared with internal temperature, i.e. the internal cell environment becomes more electronegative/electropositive in relation to the external one. Changes in temperature affected the amplitude of action potentials, measured as the voltage difference between the threshold and the peak, and their duration, measured as the width of the action potential at the threshold. As the temperature is increased, the amplitude of action potential is decreased and its duration is reduced. This parameter may influence the functioning of a neuron through the temperature dependence of ion channel conductance and time constants of channel activation/inactivation factors. Alterations in temperature affect the rates of diffusion through ion channels, the rates of conformational changes that lead to their activation and inactivation, and the rates of the biochemical reactions with which ion channels are modulated and transported into and out of membranes. Measurements of the propagated action potentials at different temperatures show that temperature has a double effect on the action potential: an increase of the Nernst equilibrium potentials when the absolute temperature is decreased and a change of the rate constants by a temperature factor. Temperature induced changes in the equilibrium potentials alone have little effect on the duration and amplitude of any action potentials but, because the cell membranes are permeable to more than one ion, the relation between the membrane potential and the Nernst equilibrium potentials shows different importance of the different ionic species in determining both resting and action potentials. In contrast, the temperature induced scaling of the rate constants can have quite dramatic effects on the duration of the action potential. As well as affecting the rate of action potential propagation, temperature influences the rate of neuron firing: the changes of action potential frequencies with temperature are associated, although not in a simple manner, with changes in resting potentials. Cooling reduces the resting potential (depolarization) and this leads to a rise in action potential frequencies; but certain nerve cells show a frequency increase when temperature is raised.

Angiotensin II type 1 receptor mediates partially hyposmotic-induced increase of I Ks current in guinea pig atrium

A repolarizing conduction in the heart augmented by hyposmotic or mechanically induced membrane stretch is the slow component of delayed rectifier K(+) current (I (Ks)). I (Ks) upregulation is recognized as a factor promoting appearance of atrial fibrillation (AF) since gain-of-function mutations of the channel genes have been detected in congenital AF. Mechanical stretch activates angiotensin II type 1 (AT(1)) receptor in the absence of its physiological ligand angiotensin II. We investigated the functional role of AT(1) receptor in I (Ks) enhancement in hyposmotically challenged guinea pig atrial myocytes using the whole-cell patch-clamp method. In atrial myocytes exposed to hyposmotic solution with osmolality decreased to 70% of the physiological level, I (Ks) was enhanced by 84.1%, the duration of action potential at 90% repolarization (APD(90)) was decreased by 16.8%, and resting membrane potential was depolarized (+4.9 mV). The hyposmotic-induced effects on I (Ks) and APD(90) were significantly attenuated by specific AT(1) receptor antagonist candesartan (1 and 5 muM). Pretreatment of atrial myocytes with protein tyrosine kinase inhibitors tyrphostin A23 and A25 suppressed but the presence of tyrosine phosphatase inhibitor orthovanadate augmented hyposmotic stimulation of I (Ks). The above results implicate AT(1) receptor and tyrosine kinases in the hyposmotic modulation of atrial I (Ks) and suggest acute antiarrhythmic properties of AT(1) antagonists in the settings of stretch-related atrial tachyarrhythmias.