Microelectrode Techniques Research Articles

Scanning glass microelectrode technique for investigating temperature-dependent electrical properties

Abstract Recent progresses in ionic current analyses related to micro- and nano-object sensing, electrochemical sensors, and liquid pollution monitoring have attracted significant attention. Micro- and nanoscale sensors with high spatial resolution and high signal-to-noise ratios are also effective for obtaining detailed understanding of ion transport phenomena. We have developed a glass microelectrode technique for measuring the electrical potential distribution by scanning through liquids. It enables us to directly evaluate electrical properties with a spatial resolution equal to the glass tip diameter, which is less than 1 μm. Herein, we optimize the channel and cell structures for the analysis of temperature-dependent properties, which allows us to measure the temperature dependence of conductivity and viscosity in the range of 303--333 K based on the Stokes--Einstein relation. The proposed method, which directly measures the spatial distribution of electrical potential, is suitable for analyzing conductivity, viscosity, and concentration without preprocessing calibration.

A Comparative Study of the Rapid (IKr) and Slow (IKs) Delayed Rectifier Potassium Currents in Undiseased Human, Dog, Rabbit, and Guinea Pig Cardiac Ventricular Preparations.

To understand the large inter-species variations in drug effects on repolarization, the properties of the rapid (IKr) and the slow (IKs) components of the delayed rectifier potassium currents were compared in myocytes isolated from undiseased human donor (HM), dog (DM), rabbit (RM) and guinea pig (GM) ventricles by applying the patch clamp and conventional microelectrode techniques at 37 °C. The amplitude of the E-4031-sensitive IKr tail current measured at -40 mV after a 1 s long test pulse of 20 mV, which was very similar in HM and DM but significant larger in RM and GM. The L-735,821-sensitive IKs tail current was considerably larger in GM than in RM. In HM, the IKs tail was even smaller than in DM. At 30 mV, the IKr component was activated extremely rapidly and monoexponentially in each studied species. The deactivation of the IKr component in HM, DM, and RM measured at -40 mV. After a 30 mV pulse, it was slow and biexponential, while in GM, the IKr tail current was best fitted triexponentially. At 30 mV, the IKs component activated slowly and had an apparent monoxponential time course in HM, DM, and RM. In contrast, in GM, the activation was clearly biexponential. In HM, DM, and RM, IKs component deactivation measured at -40 mV was fast and monoexponential, while in GM, in addition to the fast component, another slower component was also revealed. These results suggest that the IK in HM resembles that measured in DM and RM and considerably differs from that observed in GM. These findings suggest that the dog and rabbit are more appropriate species than the guinea pig for preclinical evaluation of new potential drugs expected to affect cardiac repolarization.

Elucidating the impact of non-spherical morphology on kinetic behavior of graphite using single-particle microelectrode

The precise assessment of the kinetic properties of graphite is crucial for the design of the material and the development of electrochemical models for lithium-ion batteries. However, conventional evaluation methods using composite electrodes fall short in excluding the influence of its porous structure and evaluating the influence of particle shape on kinetic behavior. In this work, we elucidate the impact of non-spherical morphology on kinetic behavior of single artificial graphite particle, employing the single-particle microelectrode technique. Three single artificial graphite particles with different sizes are pre-cycled and exhibit outstanding rate capability, maintaining a maximum capacity retention of 78.1 % at 200 C. Further, exchange current density and diffusion coefficients are determined through Tafel plots and the potentiostatic intermittent titration technique (PITT), respectively. It is found that the particle with a higher exposure of edge planes present elevated exchange current density and diffusion coefficients. Considering that the graphite particles typically feature an ellipsoidal rather than spherical shape, we propose an approach based on an ellipsoidal diffusion model for extracting diffusion coefficients. This model takes into account the non-spherical morphology of graphite, addressing the limitations inherent in the geometric assumptions of previous methods. The average relative error between the diffusion coefficients derived from the ellipsoidal diffusion model and the previous method using spherical assumptions is 215 %, indicating that accurately depicting the shape of ellipsoidal graphite particles in the model is crucial for obtaining correct estimates of kinetic parameters. This study offers direct experimental evidence of superior kinetic behavior of edge planes over basal planes. To leverage this characteristic, it is recommended to employ an out-of-plane aligned architecture for composite electrodes using novel techniques, e.g., 3D printing or magnetic alignment techniques.

ДЕЙСТВИЕ ЭКСТРАКТОВ ИЗ ARTEMİSİA L. НА ПЛАЗМАТИЧЕСКУЮ МЕМБРАНУ В УСЛОВИЯХ СТРЕССА

Plant bioactive compounds are supposed to be the modifiers of structural-functional properties of cell plasma membrane under HM contamination. To test a protective effect of extracts from Artemisia L. species, possessing high adaptive potential to different soil contaminations, on electrical properties of algae cells under HM treatments was the aim of the present work. Extracts from Artemisia plants were isolated from above-ground parts of A.scoparia and A.szovitsiana by acetone hydrolyzation. Microelectrode techniques were used to study the regularities of change of membrane potential and membrane resistance of Chara gymnophylla and Nitella flexilis plasmalemma under influence of Cd, Cu, Zn, Pb and the extracts from Artemisia species. Statistically reliable hyperpolarizing effect of A.szovitsiana and A.scoparia extracts in relation to Zn and Pb was revealed, respectively. Elimination by extracts a decrease of membrane conductivity caused by Cd and Zn and also an increase of conductivity by Cu was determined. Though a high HM accumulation capacity of Artemisia L. species is noticed to not connect with protective effect of their extracts on membrane conductivity, they can be a potential source for the searching new chemical compounds which are capable to induce the plant tolerance to stress impacts.

Cellular electrophysiological effects of the citrus flavonoid hesperetin in dog and rabbit cardiac ventricular preparations

Recent experimental data shows that hesperetin, a citrus flavonoid, affects potassium channels and can prolong the QTc interval in humans. Therefore, in the present study we investigated the effects of hesperetin on various transmembrane ionic currents and on ventricular action potentials. Transmembrane current measurements and action potential recordings were performed by patch-clamp and the conventional microelectrode techniques in dog and rabbit ventricular preparations. At 10 µM concentration hesperetin did not, however, at 30 µM significantly decreased the amplitude of the IK1, Ito, IKr potassium currents. Hesperetin at 3–30 µM significantly and in a concentration-dependent manner reduced the amplitude of the IKs current. The drug significantly decreased the amplitudes of the INaL and ICaL currents at 30 µM. Hesperetin (10 and 30 µM) did not change the action potential duration in normal preparations, however, in preparations where the repolarization reserve had been previously attenuated by 100 nM dofetilide and 1 µg/ml veratrine, caused a moderate but significant prolongation of repolarization. These results suggest that hesperetin at close to relevant concentrations inhibits the IKs outward potassium current and thereby reduces repolarization reserve. This effect in certain specific situations may prolong the QT interval and consequently may enhance proarrhythmic risk.

Microelectrode‐enabled Electrocrystallization of Cobalt TCNQ Complex for Gas Sensing

AbstractElectrocrystallization is a promising method for controlled charge‐transfer complex (CTC) deposition on microfabricated electrodes for gas sensing applications. However, there remains a gap in our understanding of CTC electrodeposition. In this study, we focus on investigating the electrocrystallization of cobalt tetracyanoquinodimethane (Co‐TCNQ) on a microdisk electrode to elucidate and control the process. Leveraging the microelectrode technique, we conduct steady‐state measurements to observe nucleation and crystal growth dynamics, particularly in the early stages of electrocrystallization. We use cyclic voltammetry and chronoamperometry to examine Co‐TCNQ electrocrystallization under various electrolytic conditions. We identify electrocrystallization kinetics, ranging from electrokinetic to diffusion‐limited growth, governing the nucleation and growth of Co‐TCNQ crystals. Notably, we pinpoint the applied overpotential and precursor concentration range necessary for a single nucleation site on the microelectrode. Moreover, we demonstrate control over crystal orientation and morphology. Our findings reveal a nonclassical growth pathway for Co‐TCNQ crystals characterized by oriented attachment of small crystallites along the conductive long axis. Importantly, electrodeposited Co‐TCNQ on patterned microelectrodes exhibits selective sensing capabilities for nitrogen dioxide gas. Overall, this study sheds light on CTC electrodeposition through a proof‐of‐concept demonstration involving Co‐TCNQ electrodeposition on microelectrodes, presenting potential applications across diverse materials.

Spatial Analysis of the Damage Zone in Double Network Hydrogel Using the Microelectrode Technique

Spatial Analysis of the Damage Zone in Double Network Hydrogel Using the Microelectrode Technique

The epithelial polarity axis controls the resting membrane potential and Cl- co-transport in breast glandular structures.

The membrane potential (MP) controls cell homeostasis by directing molecule transport and gene expression. How the MP is set upon epithelial differentiation is unknown. Given that tissue architecture also controls homeostasis, we investigated the relationship between basoapical polarity and resting MP in three-dimensional culture of the HMT-3522 breast cancer progression. A microelectrode technique to measure MP and input resistance reveals that the MP is raised by gap junction intercellular communication (GJIC), which directs tight-junction mediated apical polarity, and is decreased by the Na+/K+/2Cl- (NKCC, encoded by SLC12A1 and SLC12A2) co-transporter, active in multicellular structures displaying basal polarity. In the tumor counterpart, the MP is reduced. Cancer cells display diminished GJIC and do not respond to furosemide, implying loss of NKCC activity. Induced differentiation of cancer cells into basally polarized multicellular structures restores widespread GJIC and NKCC responses, but these structures display the lowest MP. The absence of apical polarity, necessary for cancer onset, in the non-neoplastic epithelium is also associated with the lowest MP under active Cl- transport. We propose that the loss of apical polarity in the breast epithelium destabilizes cellular homeostasis in part by lowering the MP.

Resistance of Embryonic Chick Atria to Inhibition of HCN-Channels and Components of the “Ca<sup>2+</sup>-Clock”

Despite its medical importance, the cellular mechanisms activity and the contribution of various ion channels of embryonic heart automatism are not yet fully understood. In this study we investigated the effects of specific ion-channel inhibitors on the generation of action potentials in pacemaker cells of the right atrium in chicken embryos (HH36). We used microelectrode technique and evaluated the sensitivity of pacemaker cells to ivabradine (inhibitor of HCN-channels, through which the hyperpolarization-activated current, If), ryanodine (agonist of ryanodine receptors) and SN6 (inhibitor of Na+/Ca2+-exchange). It was found that the right atrium cells have a phase of slow diastolic depolarization. However, these cells were not sensitive to ivabradine (3 μM). We did not register significant changes in the electrophysiological parameters of action potentials.When ryanodine (1 μM) and SN6 (10 μM) were added to the perfusion solution, we observed similar effects: spontaneous rate the generation of action potential increased by 15%. Disturbance of rhythmic activity or disruption of the generation of electrical impulses were not observed in right atrial samples of chicken embryos. The obtained results allow us to conclude that, at this of embryonic development stage, HCN4-channels, ryanodine receptors, and the Na+/Ca2+-exchange are not decisive for maintaining the automatism of the right atrial cells in the chick embryo. We assume that the ion currents flowing through these channels are important in electrophysiology in adult animals, but they have a modulating function in the embryonic myocardium.

Formation of neuron-microelectrode junction mediated by a synapse organizer

Neural circuits are composed of various cell types, each of which is thought to play a specific role in realizing the circuit functions. Cell-type specificity is therefore essential in recording neuronal activities but is inherently lacking in the currently available microelectrode techniques. Here, using Interleukin-1 receptor accessory protein-like 1 (IL1RAPL1) as a model synapse organizer, we show a proof-of-principle experiment that a microelectrode functionalized with a synapse organizer is capable of inducing a synapse-like junction between a neuron upon physical contact. We then discuss prospects for developing a new mode of electrophysiology that permits cell-type specific recordings via such a molecularly induced neuron-microelectrode junction.

ABT-333 (Dasabuvir) Increases Action Potential Duration and Provokes Early Afterdepolarizations in Canine Left Ventricular Cells via Inhibition of IKr.

ABT-333 (dasabuvir) is an antiviral agent used in hepatitis C treatment. The molecule, similarly to some inhibitors of hERG channels, responsible for the delayed rectifier potassium current (IKr), contains the methanesulfonamide group. Reduced IKr current leads to long QT syndrome and early afterdepolarizations (EADs), therefore potentially causing life-threatening arrhythmias and sudden cardiac death. Our goal was to investigate the acute effects of ABT-333 in enzymatically isolated canine left ventricular myocardial cells. Action potentials (APs) and ion currents were recorded with a sharp microelectrode technique and whole-cell patch clamp, respectively. Application of 1 μM ABT-333 prolonged the AP in a reversible manner. The maximal rates of phases 0 and 1 were irreversibly decreased. Higher ABT-333 concentrations caused larger AP prolongation, elevation of the early plateau potential, and reduction of maximal rates of phases 0, 1, and 3. EADs occurred in some cells in 3-30 μM ABT-333 concentrations. The 10 μM ABT-333-sensitive current, recorded with AP voltage clamp, contained a late outward component corresponding to IKr and an early outward one corresponding to transient outward potassium current (Ito). ABT-333 reduced hERG-channel-mediated ion current in a concentration-dependent, partially reversible manner with a half-inhibitory concentration of 3.2 μM. As the therapeutic plasma concentration of ABT-333 can reach the low μM range, ABT-333 application carries a risk of cardiac side effects especially in case of coadministration with strong inhibitors of CYP2C8.

Sensitization to Corrosion of Austenitic Stainless Steels: Watch Straps Intended to Come into Direct and Prolonged Contact with Skin

Nine grades of steel from different European steelmakers, namely 304L, 316L, and 904L, were evaluated. The austenitic steels studied are used in the manufacture of watch straps. The evaluations have been carried out in accordance with the ASTM standards which specifically concern the forms of corrosion, pitting (G48-11, FeCl3), intergranular (A262-15, Strauss method) test and Tuccillo–Nielsen test. The polarization electrochemical test on link watch straps was implemented by the microelectrode technique. Stress corrosion has also been investigated in the assembly of laser welded pin and link. It should be noted that, despite the fact that the grade of steel is in conformity with the classification standards, we note that the corrosion behavior is very different from one steelmaker to another. There are parameters that can change the quality of steel such as the technology process, casting volume, deoxidizers’ addition, remelted steel process and traces of pollutants. In consequence, we observe an extensive dispersion of results concerning nickel release, according to the EN 1811 European legislation regarding the protection of the population’s health, specifically relating to skin contact. In conclusion, steels DIN 1.4441 (316L Med) and DIN 1.4539 (904L) present a very good resistance to the morphologies of pitting and crevice corrosion. The 316L and 304L steel grades, also known as DIN 1.4435, DIN 1.4404 and DIN 1.4306, display a major difference in pitting and crevice corrosion behavior.

Биоэлектрические эффекты отмывания клеток Сhara fragilis от растворов фитокомпозиции одуванчик-зверобой-календулы

By using of microelectrode techniques, patterns of change in the potential (φm) and resistance (Rm) of the plasma membrane (PM) of Chara fragilis cells under the influence of Dandelion–Hypericum-Calendula (DHC) phytocomposition solutions were studied. The values of φm and Rm are widely scattered: -90 ÷ -300 mV and 1 ÷ 32.6 Ohm·m2, respectively under the standard conditions. The average value of φm was -183 ± 4.9 mV, Rm = 9.2 ± 1.2 Ohm·m2. Using the dependences of φm, Rm on the concentration of K+ in the external environment, the ranges of activation of the K+ - channels to the inward (KCİR) and outward rectification (KCOR) were determined. Under the action of the DHC phytocomposition, while the cell was in the medium with the concentration of the composite 10-1 or 1 mg/ml, we did not detect changes in φm and Rm for 25 min. Stimulation or suppression of transport processes under the influence of composites occurred only with the exclusion of DHC from the composition of the nutrient medium and with a stepwise increase in the concentration of the composition in the medium. The electrophysiological effects of the action of the DHC composition are discussed from the point of view of its action on the lipid phase of the plasma membrane of the experimental cells.

SGLT2 Inhibitor Empagliflozin Modulates Ion Channels in Adult Zebrafish Heart.

Empagliflozin, an inhibitor of sodium-glucose co-transporter 2 (iSGLT2), improves cardiovascular outcomes in patients with and without diabetes and possesses an antiarrhythmic activity. However, the mechanisms of these protective effects have not been fully elucidated. This study aimed to explore the impact of empagliflozin on ion channel activity and electrophysiological characteristics in the ventricular myocardium. The main cardiac ionic currents (INa, ICaL, ICaT, IKr, IKs) and action potentials (APs) were studied in zebrafish. Whole-cell currents were measured using the patch clamp method in the isolated ventricular cardiomyocytes. The conventional sharp glass microelectrode technique was applied for the recording of APs from the ventricular myocardium of the excised heart. Empagliflozin pretreatment compared to the control group enhanced potassium IKr step current density in the range of testing potentials from 0 to +30 mV, IKr tail current density in the range of testing potentials from +10 to +70 mV, and IKs current density in the range of testing potentials from −10 to +20 mV. Moreover, in the ventricular myocardium, empagliflozin pretreatment shortened AP duration APD as shown by reduced APD50 and APD90. Empagliflozin had no influence on sodium (INa) and L- and T-type calcium currents (ICaL and ICaT) in zebrafish ventricular cardiomyocytes. Thus, we conclude that empagliflozin increases the rapid and slow components of delayed rectifier K+ current (IKr and IKs). This mechanism could be favorable for cardiac protection.

Measurements of the light-induced steady state electric potential generation by photosynthetic pigment-protein complexes.

In this minireview, we consider the methods of measurements of the light-induced steady state transmembrane electric potential (Δψ) generation by photosynthetic systems, e.g. photosystem I (PS I). The microelectrode technique and the detection of electrochromic bandshifts of carotenoid pigments are most appropriate for Δψ measurements in situ and in vivo. Direct electrometrical method and Δψ measurements in the photovoltaic system based on membrane filter (MF) sandwiched between semiconductor indium tin oxide electrodes (ITO) are suitable for studies of isolated pigment-protein complexes and small natural vesicles-chromatophores. In the presence of trehalose, ITO|PS I-MF|ITO system allows to keep a steady state level of ∆ψ after 1h of illumination. According to preliminary experiments, this system is capable of providing steady state light-induced ∆ψ after several months of storage in the dark at room temperature under controlled humidity in the presence of trehalose. The long-term generation of light-induced ∆ψ in relatively simple system may serve as a source of the solar-to-electric energy conversion.

MicroRNA miR-133a-3p Facilitates Adrenergic Proarrhythmic Ectopy in Rat Pulmonary Vein Myocardium by Increasing cAMP Content.

Cardiac-specific microRNA miR-133a-3p modulates adrenergic signaling. Adrenergic receptors and their intracellular pathways are the key players in proarrhythmic ectopy derived from the myocardial sleeves of the pulmonary veins. We studied the effect of miR-133a-3p on ectopy induced by norepinephrine in myocardial tissue of rat pulmonary veins. Using microelectrode technique, we revealed facilitation of proarrhythmic pattern of spontaneous bursts of action potentials induced by norepinephrine in tissue preparations of the pulmonary veins isolated from rats in 24 h after injection of a transfection mixture containing miR-133a-3p (1 mg/kg) in vivo. According to ELISA data, the cAMP level in the pulmonary vein myocardium of rats receiving miR-133a-3p was 2-fold higher than in control animals. Bioinformatic analysis showed that mRNA of protein phosphatases and some phosphodiesterases are most probable targets of miR-133a-3p. The proarrhythmic effect of miR-133a-3p can be related to inhibition of the expression of phosphodiesterases accompanied by cAMP accumulation and increased intracellular β-adrenergic signaling.

In vivo and cellular antiarrhythmic and cardiac electrophysiological effects of desethylamiodarone in dog cardiac preparations.

The aim of the present study was to study the antiarrhythmic effects and cellular mechanisms of desethylamiodarone (DEA), the main metabolite of amiodarone (AMIO), following acute and chronic 4-week oral treatments (25-50 mg·kg-1 ·day-1 ). The antiarrhythmic effects of acute iv. (10 mg·kg-1 ) and chronic oral (4 weeks, 25 mg·kg-1 ·day-1 ) administration of DEA were assessed in carbachol and tachypacing-induced dog atrial fibrillation models. Action potentials were recorded from atrial and right ventricular tissue following acute (10 μM) and chronic (p.o. 4 weeks, 50 mg·kg-1 ·day-1 ) DEA application using the conventional microelectrode technique. Ionic currents were measured by the whole cell configuration of the patch clamp technique in isolated left ventricular myocytes. Pharmacokinetic studies were performed following a single intravenous dose (25 mg·kg-1 ) of AMIO and DEA intravenously and orally. In chronic (91-day) toxicological investigations, DEA and AMIO were administered in the oral dose of 25 mg·kg-1 ·day-1 ). DEA exerted marked antiarrhythmic effects in both canine atrial fibrillation models. Both acute and chronic DEA administration prolonged action potential duration in atrial and ventricular muscle without any changes detected in Purkinje fibres. DEA decreased the amplitude of several outward potassium currents such as IKr , IKs , IK1 , Ito , and IKACh , while the ICaL and late INa inward currents were also significantly depressed. Better drug bioavailability and higher volume of distribution for DEA were observed compared to AMIO. No neutropenia and less severe pulmonary fibrosis was found following DEA compared to that of AMIO administration. Chronic DEA treatment in animal experiments has marked antiarrhythmic and electrophysiological effects with better pharmacokinetics and lower toxicity than its parent compound. These results suggest that the active metabolite, DEA, should be considered for clinical trials as a possible new, more favourable option for the treatment of cardiac arrhythmias including atrial fibrillation.

Ventricular Dysfunction in Obese and Nonobese Rats with Metabolic Syndrome.

Obesity and dyslipidemias are both signs of metabolic syndrome, usually associated with ventricular arrhythmias. Here, we tried to identify cardiac electrical alteration and biomarkers in nonobese rats with metabolic syndrome (MetS), and these findings might lead to more lethal arrhythmias than obese animals. The MetS model was developed in Wistar rats with high-sucrose diet (20%), and after twenty-eight weeks were obtained two subgroups: obese (OMetS) and nonobese (NOMetS). The electrocardiogram was used to measure the ventricular arrhythmias and changes in the heart rate variability. Also, we measured ventricular hypertrophy and its relationship with electrical activity alterations of both ventricles, using micro-electrode and voltage clamp techniques. Also, we observed alterations in the contraction force of ventricles where a transducer was used to record mechanical and electrical papillary muscle, simultaneously. Despite both subgroups presenting long QT syndrome (0.66 ± 0.05 and 0.66 ± 0.07 ms with respect to the control 0.55 ± 0.1 ms), the changes in the heart rate variability were present only in OMetS, while the NOMetS subgroup presented changes in QT interval variability (NOMetS SD = 1.8, SD2 = 2.8; SD1/SD2 = 0.75). Also, the NOMetS revealed tachycardia (10%; p < 0.05) with changes in action potential duration (63% in the right papillary and 50% in the left papillary) in the ventricular papillary which are correlated with certain alterations in the potassium currents and the force of contraction. The OMetS showed an increase in action potential duration and the force of contraction in both ventricles, which are explained as bradycardia. Our results revealed lethal arrhythmias in both MetS subgroups, irrespectively of the presence of obesity. Consequently, the NOMetS showed mechanical-electrical alterations regarding ventricle hypertrophy that should be at the NOMetS, leading to an increase of CV mortality.

Inflammatory degranulation of the cardiac resident mast cells suppresses the pacemaking and affects activation pattern in the sinoatrial node

BackgroundMany bacterial and viral infections may cause sepsis or/and systemic or local proinflammatory responses that lead to life-threatening cardiovascular system failure. Severe bradycardia and/or bradyarrhythmias frequently accompany systemic inflammation and contribute to hemodynamic insufficiency. Markers for immunocompetent cells have been shown to be present in the tissue of the primary heart pacemaker, the sinoatrial node (SAN). However, the role of the resident cardiac immune cells in inflammation-induced bradycardia and SAN automaticity have still not been elucidated. Materials and methodsConfocal and bright field microscopy were used to identify toluidine blue-positive cells (TPC) in the SAN. Standard microelectrode technique and optical mapping were used to record action potentials (AP) and analyze activation pattern in the SAN tissue preparation from rats in presence of secretagogue C48/80. ResultsNumerous TPC, which exhibit toluidine-accumulating granules, typical for mast cells, are revealed in the SAN region of the right atrium. The activation and degranulation of the resident mast cells by C48/80 leads to biphasic changes of the pacemaker AP rate in the SAN – an initial acceleration is followed by rate reduction. The activation of the resident mast cells causes an increase of the primary activation area in the SAN that probably underlies the AP rate increase in response to C48/80. In addition, the application of C48/80 causes the primary/leading activation point migration in the SAN and AP rate decrease is probably mediated by the shift of the primary pacemaker site to the region surrounding the coronary sinus. Moreover, inexcitable zones and conduction blocks induced in the central SAN myocardium by C48/80 underlie the suppression of automaticity. ConclusionThe degranulation of resident mast cells affects the pacemaker cardiomyocytes’ ability to generate spontaneous AP in the SAN tissue and causes shift of the dominant pacemaker site. Therefore, the activation of the resident mast cells in the SAN can be considered as a new mechanism of inflammatory induced bradyarrhythmias.

JULIEs: nanostructured polytrodes for low traumatic extracellular recordings and stimulation in the mammalian brain

Objective. Extracellular microelectrode techniques are the most widely used approach to interrogate neuronal populations. However, regardless of the manufacturing method used, damage to the vasculature and circuit function during probe insertion remains a concern. This issue can be mitigated by minimising the footprint of the probe used. Reducing the size of probes typically requires either a reduction in the number of channels present in the probe, or a reduction in the individual channel area. Both lead to less effective coupling between the probe and extracellular signals of interest. Approach. Here, we show that continuously drawn SiO2-insulated ultra-microelectrode fibres offer an attractive substrate to address these challenges. Individual fibres can be fabricated to >10 m continuous stretches and a selection of diameters below 30 µm with low resistance (<100 Ω mm−1) continuously conductive metal core of <10 µm and atomically flat smooth shank surfaces. To optimize the properties of the miniaturised electrode-tissue interface, we electrodeposit rough Au structures followed by ∼20 nm IrOx film resulting in the reduction of the interfacial impedance to <500 kΩ at 1 kHz. Main results. We demonstrate that these ultra-low impedance electrodes can record and stimulate both single and multi-unit activity with minimal tissue disturbance and exceptional signal-to-noise ratio in both superficial (∼40 µm) and deep (∼6 mm) structures of the mouse brain. Further, we show that sensor modifications are stable and probe manufacturing is reproducible. Significance. Minimally perturbing bidirectional neural interfacing can reveal circuit function in the mammalian brain in vivo.