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Purpose: The Quality of Recovery-15 (QoR-15) tool, validated for measuring postoperative recovery following scheduled surgeries, has not been psychometrically assessed in emergency contexts. Moreover, the QoR-15’s associations with long-term outcomes remain underexplored. This study aimed to confirm the validity and reliability of the QoR-15 following emergency surgery and assess its association with three-month postoperative quality of life. Methods: We conducted a prospective cohort study (August 2021–April 2022) on adult patients who underwent emergency surgery. The QoR-15 questionnaire was administered before surgery (H0) and at 24 hr (H24) and 48 hr (H48) after surgery. We examined the H24 score’s associations with both the three-month quality of life, as assessed by the EQ-5D scale, and the number of days spent at home at 30 (DAH30) and 90 (DAH90) days. Results: Of the 375 included patients, 352 (94%) completed the QoR-15 at H24 and 338 (90%) were followed up at three months. The population represented the following diverse surgical specialties: orthopedic (51%), gastrointestinal (27%), urologic (13%), and others (9%). The QoR-15 questionnaire confirmed all psychometric qualities (internal consistency, reproducibility, responsiveness, acceptability, construct, and convergent validities) in the emergency context. The average minimum clinical difference was 8.0 at H24. There was an association between QoR-15 at H24 and the three-month quality of life (r = 0.24; 95% confidence interval [CI], 0.14 to 0.34; P< 0.001), DAH30 (r = 0.33; 95% CI, 0.23 to 0.41; P< 0.001), and DAH90 (r = 0.31; 95% CI, 0.22 to 0.40; P< 0.001). Conclusion: The QoR-15 score is valid for measuring early postoperative recovery after emergency surgery. The H24 score significantly correlated with both the three-month quality of life and the number of days at home. Study registration: ClinicalTrials.gov (NCT04845763); first submitted 11 April 2021.

The mechanisms of action of and resistance to trastuzumab deruxtecan (T-DXd), an anti-HER2–drug conjugate for breast cancer treatment, remain unclear. The phase 2 DAISY trial evaluated the efficacy of T-DXd in patients with HER2-overexpressing (n= 72, cohort 1), HER2-low (n= 74, cohort 2) and HER2 non-expressing (n= 40, cohort 3) metastatic breast cancer. In the full analysis set population (n= 177), the confirmed objective response rate (primary endpoint) was 70.6% (95% confidence interval (CI) 58.3–81) in cohort 1, 37.5% (95% CI 26.4–49.7) in cohort 2 and 29.7% (95% CI 15.9–47) in cohort 3. The primary endpoint was met in cohorts 1 and 2. Secondary endpoints included safety. No new safety signals were observed. During treatment, HER2-expressing tumors (n= 4) presented strong T-DXd staining. Conversely, HER2 immunohistochemistry 0 samples (n= 3) presented no or very few T-DXd staining (Pearson correlation coefficient r= 0.75, P= 0.053). Among patients with HER2 immunohistochemistry 0 metastatic breast cancer, 5 of 14 (35.7%, 95% CI 12.8–64.9) with ERBB2expression below the median presented a confirmed objective response as compared to 3 of 10 (30%, 95% CI 6.7–65.2) with ERBB2expression above the median. Although HER2 expression is a determinant of T-DXd efficacy, our study suggests that additional mechanisms may also be involved. (ClinicalTrials.gov identifier NCT04132960.)

Hydrocotyle bonariensisComm ex Lamm (Araliaceae) is one of these plants sufficiently exploited in traditional African medicine for its hypotensive effect. However, the pharmacological effects of those plants on cardiac functions are not well known. The potassium currents IKs and IKr, responsible for the repolarization of cardiac cell action potential, strongly influence the human cardiac rhythm. Therefore, modulators of these currents have a beneficial or undesirable medical importance in relation to cardiac arrhythmias. In order to optimize the therapeutic use of this medicinal plant, we studied the effects of hydro-ethanolic leaf extract of Hydrocotyle bonariensis on both potassium currents.

•ATM condylar orientation has been quantified using 3D modeling on 105 jaws.•Main results indicate that condyle location and orientation are highly significantly different between the left and right sides within the same mandible.•This morphologic study will enable further kinematic approches to better address the difference of motion representation observed for the right or left condyles.

Obinutuzumab monotherapy has shown promising efficacy in mantle cell lymphoma. We aimed to investigate the activity of obinutuzumab plus DHAP (dexamethasone, high-dose cytarabine, and cisplatin), measured by minimal residual disease quantitative (q)PCR status in the bone marrow after four cycles.

We examined the understanding of emotional speech by deaf children with cochlear implant (CI). Thirty deaf children with CI and 60 typically developing controls (matched on chronological age or hearing age) performed a computerized task featuring emotional prosody, either embedded in a discrepant context or without any context at all. Across the task conditions, the deaf participants with CI scored lower on the prosody-bases responses than their peers matched on chronological age or hearing age. Additionally, we analyzed the effect of age on determining correct prosody-based responses and we found that hearing age was a predictor of the accuracy of prosody-based responses. We discuss these findings with respect to delay in prosody and intermodal processing. Future research should aim to specify the nature of the cognitive processes that would be required to process prosody.

La Base de Données pour les Observatoires en Hydrologie (BDOH) est un outil de bancarisation qui permet de combiner les mesures de débit, de matières en suspension (MES) et de contaminants particulaires issues d'un même réseau de stations pour calculer des chroniques de flux instantanés et cumulés. Cette application est utilisée dans le cadre de l'Observatoire des Sédiments du Rhône (OSR) pour estimer les flux de MES et de contaminants associés (Hg, PCB,...) en transit dans le Rhône et ses principaux affluents. Cependant, avant le calcul de ces chroniques, les données mères lacunaires doivent être reconstituées. Un test de sensibilité a été mené afin d'évaluer l'impact de différentes méthodes d'estimation des chroniques de concentrations en MES et en Hg particulaire sur les calculs de flux instantanés et cumulés dans le Rhône aux deux stations principales de l'OSR (Jons et Arles). Les résultats montrent que, quelle que soit la méthode d'estimation utilisée, les flux annuels de MES et de Hg particulaire ne diffèrent pas plus de 5 %. A l'échelle mensuelle, en revanche, les différentes méthodes génèrent des variabilités plus élevées (26-51 %). En perspective, ces premiers résultats seront complétés par l'évaluation des incertitudes quantitatives sur les calculs de flux particulaires.

Optical refrigeration of a semiconductor generally requires a laser excitation very close to its bandgap and a radiative efficiency close to 1. Under these two conditions, the material can be refrigerated by radiating more energy than it absorbs. In this theoretical work, we propose considering impact ionization, which appears to be predominant in transition metal dichalcogenides and evaporative cooling to overcome both requirements. With impact ionization, high-energy photons excite multiple low-energy electron–hole pairs rather than heating the material by emitting phonons when the high-energy carriers thermalize. Thanks to an evaporative cooling effect, such low-energy electron–hole pairs diffuse from a small bandgap absorber into a larger bandgap reservoir by absorbing phonons. This cooling process operates even in materials with a modest radiative efficiency. We propose a device based on a small bandgap absorber (a strain-balanced superlattice based on two-dimensional transition metal dichalcogenides) and a larger bandgap reservoir made of bulk MoS2, forming a type I heterojunction. With a detailed balance approach, parametrized with ab initiocalculations, we demonstrate a net cooling of the absorber under solar irradiation above 25%, even considering low external radiative efficiency.

The health and equity issues related to urban pollution, coupled with the need to assess the consequences of implementing transport policies or new mobility solutions, make it imperative to provide decision-makers with a relevant modeling framework. The coupling of activity-based travel models with environmental models presents a promising approach to thoroughly investigate the interconnected issues related to the impact of road traffic on individual exposure to noise and air pollution. Integrated modeling chains provide a robust framework to comprehensively assess traffic scenarios on a city scale and address issues related to environmental inequalities. This article reviews the recent work in this field to identify both the main contributions and key challenges still to be addressed. It illustrates how the use of a dynamic approach, which considers the intraday dynamics of individual mobilities and pollution concentrations, can contribute to more accurate estimates of the exposure of individuals to pollutants. This modeling approach also has the potential to investigate how the level of exposure depends on the characteristics of the individuals (socioeconomic factors, commuting patterns, location of residence, and main activities). Nonetheless, there are still important challenges to overcome to further enhance the accuracy and applicability of these models: taking into account all types of traffic and transport modes; refining the modeling of exposure to pollution during travel; taking better consideration of microenvironments; and so forth.

We propose and numerically investigate, through a multiscale approach, a tandem solar cell based on a van der Waals heterostructure comprising of two monolayers of transition-metal dichalcogenides. The electronic connection between the two subcells is obtained via tunneling through the van der Waals heterojunction, which is electrostatically controlled by means of a dual gate. Furthermore, by adjusting the dual-gate voltages, the photocurrents in the two subcells can be matched and the tandem cell performances can be optimized. Assuming an optimal absorptance, as expected in light-trapping systems, we predict that a power conversion efficiency of 30.7%, largely exceeding that of the single subcells, can be achieved. The proposed design being suitable for other van der Waals heterojunctions shows that it represents a viable option for future high-efficiency photovoltaic systems.

La Base de Données pour les Observatoires en Hydrologie (BDOH) est un outil de bancarisation qui permet de combiner les mesures de débit, de matières en suspension (MES) et de contaminants particulaires issues d'un même réseau de stations pour calculer des chroniques de flux instantanés et cumulés. Cette application est utilisée dans le cadre de l'Observatoire des Sédiments du Rhône (OSR) pour estimer les flux de MES et de contaminants associés (Hg, PCB,...) en transit dans le Rhône et ses principaux affluents. Cependant, avant le calcul de ces chroniques, les données mères lacunaires doivent être reconstituées. Un test de sensibilité a été mené afin d'évaluer l'impact de différentes méthodes d'estimation des chroniques de concentrations en MES et en Hg particulaire sur les calculs de flux instantanés et cumulés dans le Rhône aux deux stations principales de l'OSR (Jons et Arles). Les résultats montrent que, quelle que soit la méthode d'estimation utilisée, les flux annuels de MES et de Hg particulaire ne diffèrent pas plus de 5 %. A l'échelle mensuelle, en revanche, les différentes méthodes génèrent des variabilités plus élevées (26-51 %). En perspective, ces premiers résultats seront complétés par l'évaluation des incertitudes quantitatives sur les calculs de flux particulaires.

This paper reports on MexCo (Mexico-Coventry), an ongoing online intercultural learning project underpinned by action research. Its aim is to embed internationalisation into the curriculum of the institutions involved in order to promote citizenship competences, online intercultural communicative competence in particular, among both students and staff. The integration of telecollaboration into the curriculum has highlighted problematic aspects of the development of intercultural communicative competence (ICC), such as cyberpragmatics (Yus, 2011). Cyberpragmatics is intended here as the skill of understanding others' intended meanings in computer-mediated communication. It is suggested that cyberpragmatics in online intercultural learning exchanges is a ‘Threshold Concept' (TC) (Meyer & Land, 2005, p. 375), i.e. a key concept that is troublesome to understand as it is challenging to the identity of the learner, but which could open new learning horizons to the students who do manage to grasp it.

A flexible nitride p-n photodiode is demonstrated. The device consists of a composite nanowire/polymer membrane transferred onto a flexible substrate. The active element for light sensing is a vertical array of core/shell p–n junction nanowires containing InGaN/GaN quantum wells grown by MOVPE. Electron/hole generation and transport in core/shell nanowires are modeled within nonequilibrium Green function formalism showing a good agreement with experimental results. Fully flexible transparent contacts based on a silver nanowire network are used for device fabrication, which allows bending the detector to a few millimeter curvature radius without damage. The detector shows a photoresponse at wavelengths shorter than 430 nm with a peak responsivity of 0.096 A/W at 370 nm under zero bias. The operation speed for a 0.3 × 0.3 cm2detector patch was tested between 4 Hz and 2 kHz. The −3 dB cutoff was found to be ∼35 Hz, which is faster than the operation speed for typical photoconductive detectors and which is compatible with UV monitoring applications.

This paper proposes a theoretical analysis of electronic transport in ultrathin (220 nm) single-junction GaAs solar cell. Using an in-house electronic quantum transport model, we shed light on two detrimental phenomena, namely the “backdiffusion” and the “contact-to-contact diffusion.” While the back-diffusion degrades both the short-circuit current and the fill factor, the contact-to-contact diffusion reduces the open-circuit voltage. The so-called window and back-surface-field barriers used to reflect minority carriers away from contacts reduce these two detrimental phenomena. In a second part, we then show a synthesis of performance optimization of window/GaAs/backsurface-field heterojunctions varying thicknesses, materials, and material composition profiles. Our results conclude that the Al0.4Ga0.6As(10 nm)/GaAs/In0.49Ga0.51P(10 nm) structure provides the best output power.

This study presents ionized impurity impacts on silicon nanowire MOS transistors. We calculate the current characteristics with a self-consistent three-dimensional (3D) Green’s function approach and show the effects of both acceptor and donor impurities on the physical electron properties. In particular, we emphasize that the presence of a donor induces different transport phenomena according to the applied gate bias. Our results show that the influence of a single impurity strongly depends on its position and induces high transistor performance variability with current modifications from 50% to two orders of magnitude.

3C-SiC is a promising material for high power and high-speed electronic devices as well as in sensors operating at high temperatures or hostile environments. For these reasons, we solved self-consistently the Poisson equation within the quantum Non Equilibrium Green Function Formalism (NEGF) in order to model and compare 3C-SiC and Si nanowire (NW) Field Effect Transistors (FETs) operating in ballistic regime (at room temperature 300 K). As a general conclusion of our calculations, Si and SiC NW FETs have almost the same electrical behavior: they depict the same subthreshold slope and have similar on currents [ION/IOFF (SiC)~81 % ION/IOFF (Si) in case of 4 nm NW cross section side].

A new dihydropyranone, ( R)-6-[( S)-2-hydroxy-4-(4-hydroxyphenyl)butyl]-5,6-dihydropyran-2-one ( 1), was isolated from Tapinanthus dodoneifolius.The structure was determined from spectroscopic and X-ray crystallographic analysis. Compound 1(named dodoneine) showed a relaxing effect on preconstricted rat aortic rings (IC 50of 81.4 ± 0.9 µM).

The spontaneous activity of cardiac tissue originates in specialized pacemaker cells in the sino-atrial node that generate autonomous rhythmic electrical impulses. A number of regions in the brain are also able to generate spontaneous rhythmic activity to control and regulate important physiological functions. The generation of pacemaker potentials relies on a complex interplay between different types of currents carried by cation channels. Among these currents, the hyperpolarization-activated current (termed If, cardiac pacemaker “funny” current, and Ih in neurons) is the major component contributing to the initiation of cardiac and neuronal excitability and to the modulation of this excitability by neurotransmitters and hormones. If is an inward current activated by hyperpolarization of the membrane potential and by intracellular cyclic nucleotides such as cAMP. The identification at the end of the 1990s of a family of mammalian genes that encode for four Hyperpolarization-activated Cyclic Nucleotide- gated channels, HCN1-4, has made analysis of the location of these channels and the study of their biophysical properties an obtainable goal. As a result, specific agents have been developed for their ability to selectively reduce heart rate by lowering cardiac pacemaker activity where f-channels are their main natural target. These drugs include alinidine, zatebradine, cilobradine, ZD-7288 and ivabradine. Recent data indicate that pharmacological tools such as W7 and genistein, which have been used to identify some intracellular pathways involved in ionic channel modulation, also have the ability to inhibit If directly. This opens new perspectives for the future development of other specific rhythm-lowering agents.

A method for simultaneous nondestructive evaluation of WC-Co coating thickness, elastic moduli, and density is presented. The technique, known as laser-ultrasonics, is used to generate and detect surface acoustic waves in a noncontact and nondestructive manner. The surface acoustic wave velocity dependence on frequency is compared to a model and an optimization procedure is used to evaluate the coating properties. The results obtained demonstrate the ability of the technique to simultaneously determine such properties with a single and possibly in situ measurement.

The fraction of glucose passing through glycolysis that is oxidized is low in hypertrophied hearts, a pattern of glucose use associated with poor postischemic contractile function. We tested the hypothesis that trimetazidine, a partial 3-ketoacyl coenzyme A thiolase inhibitor, would stimulate glucose oxidation and, thereby, improve fractional glucose oxidation and postischemic function of hypertrophied hearts. Function, glycolysis, and oxidation of glucose, lactate, and palmitate were measured before and after global no-flow ischemia in isolated working hearts from sham-operated (control) and aortic-constricted (hypertrophied) male Sprague-Dawley rats in the presence or absence of 1 microM trimetazidine. Heart function was significantly improved by trimetazidine after ischemia, but only in hypertrophied hearts, with function improving to values in untreated control hearts. This effect occurred in association with relatively minor changes in oxidative metabolism. However, trimetazidine reduced glycolysis by approximately 30% but did so only in hypertrophied hearts, an unexpected novel action of this agent that resulted in a larger fractional oxidation of glucose, effectively normalizing it in hypertrophied hearts. Thus, trimetazidine normalizes postischemic function and fractional glucose oxidation in hypertrophied hearts, mainly by reducing glycolysis. These data extend the potential usefulness of trimetazidine and provide support for its use as a means to improve postischemic function of pressure overload hypertrophied hearts.

In contrast to flying insects, in which distance estimation is visually mediated, self-induced image motion and use of familiar landmarks are known to play a minor role in ants. Here we show that strictly diurnal Cataglyphis cursorants can gauge with accuracy the distance they have travelled even in complete darkness in the absence of any other cues, i.e. chemical or protocounting information. Thus, an ant’s odometer is a vision-independent system based on proprioceptive cues, implicating some form of step counting, which remain to be elucidated.In contrast to flying insects, in which distance estimation is visually mediated, self-induced image motion and use of familiar landmarks are known to play a minor role in ants. Here we show that strictly diurnal Cataglyphis cursorants can gauge with accuracy the distance they have travelled even in complete darkness in the absence of any other cues, i.e. chemical or protocounting information. Thus, an ant’s odometer is a vision-independent system based on proprioceptive cues, implicating some form of step counting, which remain to be elucidated.

Heart failure is known for alteration of cardiac catecholamine responsiveness involving adrenergic receptor (AR) down-regulation. Trimetazidine, a metabolically active anti-ischemic drug, accelerates the turnover of phospholipids. The present study evaluated the consequences of trimetazidine treatment (supposed to increase phospholipid synthesis) on AR in heart failure in rats. In control rats, trimetazidine (7.5 mg/day supplied in the diet) induced after 8 weeks a significant increase in both beta- (+54%) and alpha-AR (+30%) density, although after 12 weeks, the receptor density was normalized. Heart failure was obtained by ascending aortic banding. These heart failure rats developed a severe cardiac hypertrophy, mainly affecting the left ventricle, which was significantly reduced in the trimetazidine-treated group. The plasma level of brain natriuretic peptide (BNP), a marker of heart failure severity, was significantly increased in the heart failure group as compared with the sham group (900 and 1200% after 8 and 12 weeks, respectively). In the trimetazidine-treated group, the plasma BNP increase was significantly lower. The development of heart failure was associated with a decrease in beta- and alpha-AR sites (-23 and -36% versus sham, respectively) after 8 weeks and continued to decrease after 12 weeks (-37 and -48% versus sham, respectively). This down-regulation was prevented by trimetazidine without alteration in affinity. These results suggest that trimetazidine prevents AR desensitization and cardiac hypertrophy, in a pressure-overload model of heart failure. This cytoprotection suggests that membrane homeostasis preservation may be considered as a therapeutic target in the treatment of heart failure.

Increased levels of the physiological amino acid homocysteine (Hcy) are considered a risk factor for vascular disease. Hyperhomocysteinemia causes an intense remodelling of the extracellular matrix in arterial walls, particularly an elastolysis involving metalloproteinases. We investigated the activation of the latent elastolytic metalloproteinase proMMP-2 (72 kDa) by Hcy. Hcy was proved to exert a dual effect, activating proMMP-2 at low molar ratio (MR 10:1) and inhibiting active MMP2 at high molar ratio (MR > 1000:1). Methionine and the disulphide homocystine did not activate nor inhibit MMP-2, showing that the activation as well as the inhibition requires the thiol group to be free. The activation of proMMP-2 by Hcy is in accordance with the “cysteine-switch” mechanism, but occurs without further autoproteolysis of the enzyme molecule. In contrast with Hcy, the other physiological thiol compounds cysteine and reduced glutathione did not activate proMMP-2. These results suggest that the direct activation of proMMP2 by Hcy could be one of the mechanisms involved in the extracellular matrix deterioration in hyperhomocysteinemia-associated arteriosclerosis.

Over the past three decades satellite-based remote sensing has developed from experimental programmes to a user-oriented commercial industry. The current success and future of the industry are dependent on both the commercial perspective and the advanced technical capabilities as exemplified in the SPOT system. As the U.S.A. has the largest and most advanced user community in the world, the SPOT programmes, commercial experience and resultant industry trends seen in that country are indicative of, and setting the standards for, industry development in the rest of the world.

The mechanism of the action of acetylcholine (ACh) on the L-type calcium current (ICa,L) was examined using a whole-cell voltage-clamp technique in single sino-atrial myocytes from the rabbit heart. ACh depressed basal ICa,L at concentrations in the range 0.05–10 µM, without previous ß-adrenergic stimulation. The ACh-induced reduction of ICa,L was reversed by addition of atropine, indicating that muscarinic receptors mediate it. Incubation of cells with a solution containing pertussis toxin led to abolition of the ACh effect, suggesting that this effect is mediated by G proteins activated by muscarinic receptors. Dialysis of cells with protein kinase inhibitor or 5'-adenylyl imidodiphosphate, inhibitors of the cAMP-dependent protein kinase, decreased basal ICa,L by about 85% and suppressed the effect of ACh. The ACh effect was also absent in cells dialysed with a non-hydrolysable analogue of cAMP, 8-bromo-cAMP. The results suggest that, in basal conditions, a large part of the L-type calcium channels should be phosphorylated by protein kinase A stimulated by a high cAMP level correlated with a high adenylate cyclase activity. The depressing effect of ACh on ICa,L may occur via inhibition of the high basal adenylate cyclase activity leading to a decrease of cAMP-dependent protein kinase stimulation and thus to a dephosphorylation of calcium channels.

Hyperhomocysteinemia is a risk factor for arterial diseases, and the deterioration of the arterial elastic structures is one of the possible mechanisms underlying this epidemiological association. The aim of this paper is to quantitively characterize such structural alterations and to explore their causes in a previous model of dietary induced mild hyperhomocysteinemia in minipigs. After four months, both a morphodensitometrical analysis of the elastic structure and a biochemical analysis of elastin and elastase activities were performed on the infrarenal abdominal aorta (IRAA) and the proximal left interventricular coronary artery (LIVCA) of control (C), hyperhomocysteinemic (H) and captopril-hydrochlorothiazide (Cp-Htz, 25 + 12.5 mg/d)-treated (H+Cp) minipigs ( n = 8/group ). Hyperhomocysteinemia was found to induce an increase in parietal elastolytic metalloproteinase activities. It resulted in opening and enlargement of fenestrae through the medial elastic laminae and in a decrease in medial elastin content ( p < 10 ), expressed as well as volume density (%) as weight concentration (μg elastin/mg dry tissue). The thickness of the media and its basic lamellar organization was unchanged. The reduction in volume density was more dramatic in LIVCA ( H : 4.7 ± 0.9 vs C : 8.8 ±2.4 ), where it was evenly distributed within media, than in IRAA ( H : 6.7 ± 1.1 vs C : 9.3± 1.2 ), where the deep media layers were less affected. Cp-Htz partly prevented the hyperhomocysteinemia-induced reduction of the medial elastin content LIVCA ( 5.7 ± 1.2 ) and IRAA ( 7.9 ± 1.4 ). This effect, occurring in the subintimal layers of the media in both arteries but not in the deeper layers, resulted in a less beneficial effect in LIVCA than in IRAA. This result parallels the moderate beneficial therapeutic effect of ACE inhibitors against coronary atherosclerosis in humans.

Ultrasonic waves are generated through a composite material by means of a noncontact technique. It uses a Nd:Yag LASER for the generation and an interferometric probe for the detection of acoustic waveforms. From a suitable set of experimental data, an inversion scheme is used for the recovering of four stiffness coefficients. They characterize the elasticity in a principal plane of symmetry of the material which exhibits an orthorhombic symmetry. The measurements are performed at various temperatures, elevated by steps up to 300°C for two specimen. The sensitivity of the method appears convenient to measure the temperature induced stiffness changes. The anisotropic degradation of the material properties are then pointed out.

Single sino-atrial cells from rabbit heart were voltage-clamped using the whole-cell configuration of the patch clamp technique under conditions in which most of the ionic and exchange currents known in pacemaker cardiac cells were minimized. Extracellular angiotensin II (AII) activated a time-independent background current. The current-voltage relation of this current showed an outward rectification. The reversal potential was -20 mV with 156 mm Cl- external solution and 54 mm Cl- internal solution. This reversal potential shifted with changes in the transmembrane Cl- gradient in the fashion expected for a chloride current. Anthracene-9-carboxylic acid and diphenylamine 2-carboxilic acid (chloride channels blockers) were found to be effective in blocking the AII-sensitive current. The linear segment of the current-voltage relation can be totally inhibited by the competitive AII-receptor (AT1) antagonist losartan and by the presence of intracellular protein kinase C inhibitor, whereas the outward rectification is only slightly changed. It is concluded that sino-atrial cells should contain protein-kinase-C-sensitive chloride channels which may be activated by angiotensin II via the stimulation of the AT1 receptors.