Effect of ivabradine on hyperpolarization activated cation current in canine pulmonary vein sleeve cardiomyocytes with atrial fibrillation

Objective To study the effect of ivabradine on hyperpolarization activated cation current in canine pulmonary vein(PY) sleeve cardiomyocytes with atrial fibrillation.Methods Dissociation of PVs yielded single cardiomyocytes from a Landengorff column without or with pacemaker activity from long-term rapidly atrial pacing (RAP) canines.If current was measured with the whole-cell patch-clamp technique.Results Compared with the control group,the rapidly atrial pacing canine PV cardiomyocytes had spontaneous diastolic depolarization and had larger If densities.Ivabradine (Iva,1 μM),a selective inhibitor of the If current,markedly reduced If currents in the RAP from -2.66±0.4 pA/pF to -1.58±0.1 pA/pF at the test potential of-120 mV (P＜0.01,n=12).Inhibition effect of Iva of If current showed concentration-dependent range from 0.1 to 10.0μM,with IC50 of 2.2 μ M ( 1.8-2.9 μM,95% CL).Furthermore,V1/ of steady-state activated curve was shifted from -84.3±4.9 mV to -106.9±3.4 mV and k value of steady-state activated curve was changed from 12.1+2.6 mV to 9.9±3.4 mV by the application of.1.0 μM Iva ( P＜0.01,n=12).Conclusions Our study revealed that Ivarbadine may significantly decrease If of rapidly atrial pacing pulmonary vein sleeve ceUs with atrial fibdllation.(J Geriatr Cardiol 2008;5:39-42)

After hyperpolarization of relay neurons in lateral geniculate nucleus of cat

The action potential （Na+ spike） of neurons is often followed by a compound after hyperpolarization （AHP） which is mediated by Ca2+-dependent K+ channels. Pyramidal cells in the cerebral cortex are known to have fast, medium and slow AHPs. It is commonly accepted that the fast AHP （fAHP） is mediated by a kind of C- or BK-K+ channels. The fAHP is characterized by a short duration of about 20 ms, its remarkable voltage dependence and sensitivity to low concentration （【1 mmol/L） of Tetraethylammonium （TEA）.The mAHP results from activation of AHP- or SK-K+ channels and has a long duration over 200 ms. It is poorly voltage-dependent and blocked by Apamin, but not by TEA.

Reduced expression of SK3 and IK1 channel proteins in the cavernous tissue of diabetic rats

The small （SK3） and intermediate （IK 1） conductance calcium-activated potassium channels could have key roles in the endothelium-dependent hyperpolarization factor pathway, which is believed to contribute to normal penile erection function. We aimed to investigate the expression of SK3 and IK1 in diabetic rodents. The experimental diabetes model was induced in 8-week-old male Sprague-Dawley rats （250-300 g） by a single administration of streptozotocin. Both the diabetes mellitus group （DM group, n = 20） and the control group （NDM group, n = 10） were injected with a low dose of apomorphine to allow for the measurement and comparison of the corresponding penile erections. The mRNA and protein expression levels of SK3 and IK1 were measured by reverse transcription polymerase chain reaction and western blot, respectively. Erectile function was significantly decreased in the DM group compared with control group （P 〈 0.05）. The mRNA and protein expression levels of SK3 and IK1 were reduced in the cavernous tissue of diabetic rats compared with the control group （P 〈 0.05）. Diabetes inhibits mRNA and protein expression of both SK3 and IK1 in the cavernous tissue of diabetic rats. This could play a key role in the development of erectile dysfunction in diabetic rats.

General anesthesia mediated by effects on ion channels

Although it has been more than 165 years since the first introduction of modern anesthesia to the clinic, there is surprisingly little understanding about the exact mechanisms by which general anesthetics induce unconsciousness. As a result, we do not know how general anesthetics produce anesthesia at different levels. The main handicap to understanding the mechanisms of general anesthesia is the diversity of chemically unrelated compounds including diethyl ether and halogenated hydrocarbons, gases nitrous oxide, ketamine, propofol, benzodiazepines and etomidate, as well as alcohols and barbiturates. Does this imply that general anesthesia is caused by many different mechanisms? Until now, many receptors, molecular targets and neuronal transmission pathways have been shown to contribute to mechanisms of general anesthesia. Among these molecular targets, ion channels are the most likely candidates for general anesthesia, in particular γ-aminobutyric acid type A, potassium and sodium channels, as well as ion channels mediated by various neuronal transmitters like acetylcholine, amino acids amino-3-hydroxy-5-methyl-4-isoxazolpropionic acid or N-methyl-D-aspartate. In addition, recent studies have demonstrated the involvement in general anesthesia of other ion channels with distinct gating properties suchas hyperpolarization-activated, cyclic- nucleotide-gated channels. The main aim of the present review is to summarize some aspects of current knowledge of the effects of general anesthetics on various ion channels.

Dual face of axonal inhibitory inputs in the modulation of neuronal excitability in cortical pyramidal neurons

Limited by the tiny structure of axons,the effects of these axonal hyperpolarizing inputs on neuronal activity have not been directly elucidated.Here,we imitated these processes by simultaneously recording the activities of the somas and proximal axons of cortical pyramidal neurons.We found that spikes and subthreshold potentials propagate between somas and axons with high fidelity.Furthermore,inhibitory inputs on axons have opposite effects on neuronal activity according to their temporal integration with upstream signals.Concurrent with somatic depolarization,inhibitory inputs on axons decrease neuronal excitability and impede spike generation.In addition,following action potentials,inhibitory inputs on an axon increase neuronal spike capacity and improve spike precision.These results indicate that inhibitory inputs on proximal axons have dual regulatory functions in neuronal activity（suppression or facilitation）according to neuronal network patterns.

Novel Bioelectric Mechanisms and Functional Significance of Peripheral and Central Entrainment by Respiration

The human organism is a complex biological system with emergent properties that arise from the unified functional interactions among its diverse components. When studying the brain and body in light of modern biological systems approaches, one must analyze them in a holistic manner, putting aside reductionist models in order to understand how certain properties manifest from complex system interactions. The respiratory system is capable of continuously adapting to changes in the internal and external environment, making it one of the most integrated of physiological processes. We propose an additional respiratory process: respiration-derived electrical currents during inspiration that spread throughout the entire body maintaining homeostasis through entraining oscillatory activity, modulating cognitive processes, and modulating the autonomic nervous system. If these currents are indeed created in part from redox reactions occurring on a massive scale, then we assert they are a major aspect of an embodied cognitive framework. We propose that this potentially major source of organism integrity has been overlooked, and its application to medicine could drastically change how we understand human physiology, the autonomic nervous system, and the therapeutic treatment of various clinical disorders.

On the Two Successive Supercold Waves Straddling the End of 2020 and the Beginning of 2021

Two supercold waves straddling 2020 and 2021 successively hit China and caused record-breaking extremely low temperatures.In this study,the distinct features of these two supercold waves are analyzed on the medium-range time scale.The blocking pattern from the Kara Sea to Lake Baikal characterized the first cold wave,while the large-scale tilted ridge and trough over the Asian continent featured the second cold wave.Prior to the cold waves,both the northwest and hyperpolar paths of cold air contributed to a zonally extensive cold air accumulation in the key region of Siberia.This might be the primary reason why strong and extensive supercold waves occur even under the Arctic amplification background.The two cold waves straddling 2020 and 2021 exhibited distinct features:(1)the blocking circulation occurred to the north or the east of the Ural Mountains and was not confined only to the Ural Mountains as it was for the earlier cold waves;(2)the collocation of the Asian blocking pattern and the polar vortex deflection towards East Asia preferred the hyperpolar path of cold air accumulation and the subsequent southward outburst;and(3)both high-and low-frequency processes worked in concert,leading to the very intense cold waves.The cold air advance along the northwest path,which coincides with the southeastward intrusion of the Siberian High(SH)front edge,is associated with the high-frequency process,while the cold air movement along the hyperpolar path,which is close to the eastern edge of the SH,is controlled by the low-frequency process.

Evaluation of injuries caused by coronavirus disease 2019 using multi-nuclei magnetic resonance imaging

The ongoing pandemic of coronavirus disease 2019(COVID-19)has been a great burden for the healthcare system in many countries because of its high transmissibility,severity,and fatality.Chest radiography and computed tomography(CT)play a vital role in the diagnosis,detection of complications,and prognostication of COVID-19.Additionally,magnetic resonance imaging(MRI),especially multi-nuclei MRI,is another important imaging technique for disease diagnosis because of its good soft tissue contrast and the ability to conduct structural and functional imaging,which has also been used to evaluate COVID-19-related organ injuries in previous studies.Herein,we briefly reviewed the recent research on multi-nuclei MRI for evaluating injuries caused by COVID-19 and the clinical 1 H MRI techniques and their applications for assessing injuries in lungs,brain,and heart.Moreover,the emerging hyperpolarized 129Xe gas MRI and its applications in the evaluation of pulmonary structures and functional abnormalities caused by COVID-19 were also reviewed.

A novel NMR instrument for the in-situ monitoring of the absolute polarization of laser-polarized 129Xe

A new fully digital and home-built NMR (Nuclear Magnetic Resonance) spectrometer working at very-low magnetic field (4.5 mT) is presented. This spectrometer was initially dedicated for the in situ measurement of the absolute polarization of hyperpolarized 129Xe. It allows detection and acquisition of NMR signals of proton (1H) at 190 kHz and of hyperpolarized xenon-129 (HP 129Xe) at 50 kHz. In this new NMR instrument, we replaced as much analog electronics as possible by digital electronic and software. Except for the power amplifier and the preamplifier, the whole system is digital. The transmitter is based on the use of a Direct Digital Synthesizer (DDS) board. The receiving board allows direct digitalization of the NMR signals thanks to an 8-bits analog-to-digital converter (ADC) clocked at 100 MHz. Decimation is preformed to dramatically improve the ADC resolution so as the final achieved effective resolution could be as high as 14-bits at 5 MHz sampling frequency. NMR signals are then digitally downconverted (DDC). Low-pass decimation filtering is applied on the base-band signals (I/Q) to enhance much more the dynamic range. The system requires little hardware. The transmitter and the receiver are controlled using Labview environment. It is a versatile, flexible and easy-to-replicate system. This was actually one of underlying ideas behind this development. Both 1H and hyperpolarized 129Xe NMR signals were successfully acquired. The system is used for the measurement of the absolute polarization of hyperpolarized 129Xe in hyperpolarizing experiments for the brain perfusion measurements. The high degree of flexibility of this new design allows its use for a large palette of other potential applications.

Human Pulmonary Hyperpolarized ^(129)Xe MRI: a Preliminary Study

We study the feasibility and safety of human lung hyperpolarized（HP）^（129）Xe magnetic resonance imaging（MRI）.There is no significant change in physiological parameters before and after the examinations of all subjects.Compared with computed tomography, HP^（129）Xe MRI is sensitive to earlier and smaller ventilation defects. The distribution of the HP^（129）Xe MRI signal reflects the pulmonary compliance with the gravity gradient. This is the first application of HP^（129）Xe MRI ventilation imaging in China, and this technology is expected to provide more useful information for clinical practice.

Protective Effects of Hyperpolarizing Cardioplegia with Pinacidil on Myocardium in Rats

Whether the ATP sensitive potassium channel opener pinacidil can provide myocardial protective effects in prolonged isolated global ischemic rat heart was investigated. On modified isolated rat working heart model, 40 hearts were divided into four groups randomly: Hyperpolarized arrest H K solution containing pinacidil (50 μmol/L) (P1 and P2) and depolarized arrest St. Thomas' solution (S1 and S2) subjected to 15 ℃ hypothermia, 60 min (P1 and S1) or 120 min (P1 and S2) of ischemia and 30 min reperfusion. The experimental indices included cardioplegic efficiency, cardiac function, coronary blood flow, myocardial enzyme release, myocardial water and ATP content. Hyperpolarized arrest provided significantly better recovery of cardiac function than depolarized arrest. Postischemic coronary flow and myocardial ATP content were higher. The arrest time of electro mechanical activities were longer than depolarized arrest. There were no differences among the groups in myocardial water contents. The hyperpolarized arrest solution containing pinacidil can provide a marked myocardial protective effect during prolonged hypothermic myocardial ischemia.

Design and development of a new dedicated RF sensor for the MRI of rat brain

The design and development of a new dual-frequency RF probe-head are presented. This probe was initially dedicated for the MRI of both proton (1H) and hyperpolarized Xenon-129 (HP 129Xe) in the rat brain at 2.35 Tesla. It consists of a double-tuned (100 MHz- 27.7 MHz) volume coil, which could be used for both transmitting and receiving, and of a receive-only single-tuned (27.7 MHz) coil. The double-tuned coil consists of two concentric birdcage resonators. The inner one is a low-pass design and it is tuned to 27.7 MHz, while the outer one, tuned to 100 MHz, is high-pass. The receive-only coil is a surface coil which is decoupled from the double-tuned volume coil by an active decoupling circuitry based on the use of PIN diodes. A home-built Transmit/Receive (T/R) driver ensures biasing of the PIN diodes in both volume and surface coils. The original concepts of the design are addressed, and practical details of realization are presented. One of the underlying ideas behind this work is to proceed well beyond the application to the MRI of HP 129Xe. Actually, this design could be easily adapted for a large palette of other MRI applications. Indeed, we tried to make the design versatile, simple and easy to replicate by other research groups, with a low-cost, minimum development time and accepted performances. The prototype was validated at 100 MHz and at 26.4 MHz (sodium-23 resonance frequency at 2.35 T). MRI experiments were performed using phantoms. In vivo 1H images and 23Na spectra of the rat brain are also presented.

Myocardial protection with pinacidil induced hyperpolarized arrest during cardiopulmonary bypass

Objective To investigate the myocardial protective effects of pinacidil induced hyperpolarized arrest and compare with those afforded by conventional depolarized hyperkalemic arrestMethods Eighteen dogs were equally divided into three groups: normothermic hyperpolarized group (Group A), hypothermic hyperpolarized group (Group B), and hyperkalemic group (Group C) Pinacidil (50μmol/L) containing 37℃ St Thomas solution (K+5mmol/L, 10ml/kg), pinacidil (50μmol/L, Sigma, USA) containing 4℃ St Thomas solution (K+ 5mmol/L, 10ml/kg) and 4℃ standard St Thomas solution (K+ 16mmol/L, 10ml/kg) were infused respectively through the aortic root after aorticclamping Heart arrest and its recovery, ultrastructure of the myocardium, the level of serum myocardial enzymes, and lipid peroxide and adenine cleotide of the myocardium were measuredHemodynamics during ischemia and after reperfusion were observedResults The percentages of normal mitochondria and glycogen did not change much during ischemia (except at 60 min) and after reperfusion in B Group, but declined markedly in Group C 30 min and 60 min after ischemia and 20 min after reperfusion (P<0.01) In Group A,they were lower than those of Group B before ischemia, but higher than those of Group C The recoveries of CO, SV, CI, LVSW, RVSW and MAP in Group B were significantly better than those in other two groups 15 min and 30 min after reperfusion (P<0.05and0.01, respectively) However, they were still better in Group A than those in Group C(P<0.05 and 0.01, respectively)The onset of heart arrest was faster in Groups C and B than that in Group A Highly elevated serum myocardial enzymes were observed 60 min after ischemia and 20 min after reperfusion in Group C, while they were only mild in the hyperpolarized groups, especially in Group B, and their recoveries were rapid Adenine nucleotides of the myocardium were better preserved in Group B than in other two groups 30 min, 60 min after ischemia, and 20 min after reperfusion (P<0.05 and 0.01, respectively)They were also much better in Group A than in GroupC(P<0.05and0.01,respectively)Lipid peroxide of the myocardium were significantly lower in Group B than in other groups 20 min after reperfusion (P<0.01),and they were lower in Group A than in Group C(P<0.05) Conclusions Myocardial protection for global ischemia during cardiopulmonary bypass (CPB) could be achieved with hyperpolarized heart arrest induced by pinacidil, an ATP sensitive potassium channel opener,especially in the hypothermic state The protection is weaker in normothermia but is still superior to that with traditional depolarized hyperkalemic arrest

Nanodiamonds as nanomaterial for biomedical field

Recent advances in nanotechnology have attracted significant attention to nanodiamonds(NDs)in both industrial and research areas thanks to their remarkable intrinsic properties:large specific area,poor cytotoxicity,chemical resistance,magnetic and optical properties,ease of large-scale production,and surface reactivity make them suitable for numerous applications,including electronics,optics,sensors,polishing materials,and more recently,biological purposes.Growing interest in diamond platforms for bioimaging and chemotherapy is observed.Given the outstanding features of these particles and their ease of tuning,current and future applications in medicine have the potential to display innovative imaging applications and to be used as tools for monitoring and tracking drug delivery in vivo.

Plasmalemma hyperpolarity and culture of sense and antisense abp transgenic tobacco protoplasts

The relationship among transfer and expression of auxin binding protein gene ( abp ), auxin (NAA) induced plasmalemma hyperpolarity and sensibility to auxin during protoplast culture was studied by measuring transmembrane potential difference (Em) and culturing the protoplasts of sense and antisense abp transgenic tobacco. The concentration of NAA inducing the highest degree of hyperpolarity of sense abp transgenic tobacco protoplasts was lower than the control, and in protoplast culture, their sensibility to auxin increased. The concentration of antisense abp transgenic tobacco protoplasts was higher than the control, and in protoplast culture, their sensibility to auxin decreased. These results demonstrated that ABP synthesized in endoplasmic reticulum needed to transport to cell membrane and functioned there.

The role of water in methane adsorption and diffusion within nanoporous silica investigated by hyperpolarized 129Xe and 1H PFG NMR spectroscopy

Understanding the properties and behavior of water molecules in restricted geometries, such as the nanopores of rocks, is of interest for shale gas exploitation. We present herein ex situ and in situ nuclear magnetic resonance （NMR） studies on the effects of water on the adsorption and diffusion of methane in nanopores. Silica materials with one-dimensional pores of ZSM-22, MCM-41, and SBA-15, with pore sizes ranging from 0.5 to 6 nm, were chosen as models. Hyperpolarized （HP） 129Xe NMR results show that water adsorption does not affect the pore sizes of ZSM-22 and MCM-41 but reduces that of SBA-15. The presence of water suppresses methane adsorption; this suppression effect is stronger in smaller pores. The self-diffusion coefficients of methane within ZSM-22 and MCM-41 are not significantly influenced by the presence of water, as measured by ~H pulsed field gradient （PFG） NMR. However, within SBA-15, which has a pore size of 6 nm, the diffusion coefficient of methane increases as the amount of water adsorption increases, peaks, and then decreases to a constant value with further water adsorption. These experiments reveal the effects of the pore size and the presence of water on methane adsorption and diffusion in constrained spaces, which could have important implications for flow simulations of methane in shales.