Neural Mechanisms Underlying the Coughing Reflex / 神经科学通报·英文版

Breathing is an intrinsic natural behavior and physiological process that maintains life. The rhythmic exchange of gases regulates the delicate balance of chemical constituents within an organism throughout its lifespan. However, chronic airway diseases, including asthma and chronic obstructive pulmonary disease, affect millions of people worldwide. Pathological airway conditions can disrupt respiration, causing asphyxia, cardiac arrest, and potential death. The innervation of the respiratory tract and the action of the immune system confer robust airway surveillance and protection against environmental irritants and pathogens. However, aberrant activation of the immune system or sensitization of the nervous system can contribute to the development of autoimmune airway disorders. Transient receptor potential ion channels and voltage-gated Na+ channels play critical roles in sensing noxious stimuli within the respiratory tract and interacting with the immune system to generate neurogenic inflammation and airway hypersensitivity. Although recent studies have revealed the involvement of nociceptor neurons in airway diseases, the further neural circuitry underlying airway protection remains elusive. Unraveling the mechanism underpinning neural circuit regulation in the airway may provide precise therapeutic strategies and valuable insights into the management of airway diseases.

IL-6 exacerbates potential arrhythmia of Chan Su intravenous injection / 中国药理学通报

Aim To explore the arrhythmic risk of Chan Su intravenous injection(CS)and its underlying mechanismin in the absent or presence of IL-6.Methods The recording techniques of guinea pig in vivo ECG, the action potential, L-type Ca2+ and Na+ currents from left ventricular myocytes were used to analyze heart rate(HR), P-R, QRS and QTc intervals and the underlying mechanism.Results① CS at one time CRD(clinically relevant dose)insignificantly changed the guinea pig in vivo ECG.However, the IL-6(18.4 μg·kg-1)only and the combinational use of IL-6(18.4 μg·kg-1)plus CS(one time CRD)remarkably prolonged the P-R and QTc intervals.② The CS at one time CRC(clinically relevant concentration)had no significant change in the action potential duration at 90% repolarization level(APD90).The IL-6(20 μg·L-1)only and the combination of CS at one time CRC plus IL-6(20 μg·L-1)significantly prolonged APD90.③ Moreover, the IL-6(20 μg·L-1)combined with CS at one time CRC significantly inhibited the L-type Ca2+ current. CS at one, five, ten time CRC, IL-6(20 μg·L-1)alone and IL-6(20 μg·L-1)combined with CS had no significant effects on Na+current.Conclusions CS intravenous injection has low risk of arrhythmia in the clinical settings.However, in presence of high titer of IL-6 characterized by inflammation, CS may induce the atrioventricular conduction block due to the blockade effect on Ca2+ current by both of CS and IL-6.

Cloning and expression of recombinant BmkNaTx12, a new voltage-gated sodium channel from scorpion Buthus martensii Karsch / 中国药科大学学报

A cDNA library was constructed from glands of wild Buthus martensii Karsch scorpion.A new sodium channel long-chain toxin BmkNaTx12 was identified by sequence alignment,and its full-length cDNA sequence was cloned.Sequence alignment showed that the sequence of BmkNaTx12 had high structural similarity with the β-toxin Cn12 from Mexican Centruroides noxius scorpion.The predicted structure of BmkNaTx12 was obtained by homologous model construction and the highest scoring model was selected.The protein structure was found to be stable at 300 ns by molecular dynamics optimization,and fluctuations at amino acids 20,35,and 52 are most like-ly due to the location of these amino acids in the loop region.Then,an expression system of recombinant BmkNaTx12-Fc fusion protein was constructed.The optimal expression time of recombinant protein was determined by Western blot and the fusion protein was successfully expressed in HEK293 cells.The purity of recombinant fusion protein which was obtained by protein A affinity chromatography was up to 95％ by SDS-PAGE gel electrophoresis and HPLC.In addition,the whole-cell patch-clamp assay results suggest that 1 μmoL/L BmkNaTx12-Fc can increase 20％ Nav1.7 peak current.These results laid a foundation for the further study of biological function.

Acute Hypoxia Activates an ENaC-like Channel in Rat Pheochromocytoma (PC12) Cells

Cells can resist and even recover from stress induced by acute hypoxia, whereas chronic hypoxia often leads to irreversible damage and eventually death. Although little is known about the response(s) to acute hypoxia in neuronal cells, alterations in ion channel activity could be preferential. This study aimed to elucidate which channel type is involved in the response to acute hypoxia in rat pheochromocytomal (PC12) cells as a neuronal cell model. Using perfusing solution saturated with 95% N2 and 5% CO2, induction of cell hypoxia was confirmed based on increased intracellular Ca2+ with diminished oxygen content in the perfusate. During acute hypoxia, one channel type with a conductance of about 30 pS (2.5 pA at -80 mV) was activated within the first 2~3 min following onset of hypoxia and was long-lived for more than 300 ms with high open probability (Po, up to 0.8). This channel was permeable to Na+ ions, but not to K+, Ca+, and Cl- ions, and was sensitively blocked by amiloride (200 nM). These characteristics and behaviors were quite similar to those of epithelial sodium channel (ENaC). RT-PCR and Western blot analyses confirmed that ENaC channel was endogenously expressed in PC12 cells. Taken together, a 30-pS ENaC-like channel was activated in response to acute hypoxia in PC12 cells. This is the first evidence of an acute hypoxia-activated Na+ channel that can contribute to depolarization of the cell.

Oral ranolazine in the conversion of paroxysmal and initial onset atrial fibrillation.

Background: Atrial fibrillation (AF) is the most common arrhythmia requiring treatment. High-dose oral anti-arrhythmics (mainly class 1C or quinidine) are used as “pill in the pocket” approach to convert recent onset AF. However pro-arrhythmic risk has limited the application of this approach in many patients. Ranolazine, an antianginal agent, which inhibits abnormal late Na+ channel currents, decreases sodium-calcium overload, potentially inhibits after-depolarisations which have been implicated in the initiation and propagation of AF. Methods: Two gramme ranolazine was given orally to 40 patients with new (first detected episode of AF, 16 patients) or paroxysmal (3 hours to 72 hours duration, 24 patients) AF. Twenty-four patients were in hospital, 6 in office, and 10 at home at the time of ranolazine administration. Age, sex, associated health condition, structural heart disease (SHD) and echocardiographic criteria were recorded. Treatment for other related conditions was also given. Successful conversion was defined as restoration of sinus rhythm within 6 hours of ranolazine administration. Results: Twenty-six of 40 patients (65%) converted to sinus rhythm. No pro-arrhythmic effects, haemodynamic instability, adverse effects, or perceived intolerance were noted. Conclusion: High-dose oral ranolazine shows utility as a possible safe agent to convert new or paroxysmal AF.

Effects of Low Level Laser Irradiation on Properties of Sodium Channel in Rat Hippocampal Neurons / 生物化学与生物物理进展

0.05). - 40 mV activated threshold potential and - 30 mV peak potential for control group respectively droppedto - 60 mV and - 40 mV after irradiating 7 min. The half-activation voltage and the slope factor of the activationcurves of Na+ channel were also changed by the laser's exposure. The former changed from (- 42.091 ?1.537) mVto (54.971 ?1.846) mV (n= 8, P

EFFECTS OF BTHP ON ACTION POTENTIAL OF TOAD SCIATIC NERVES / 中国药理学通报

Benzyltetrahydropalmatine ( BTHP ) which is a derivative of tet-rahydropalmatine, induced concentration-dependent decreases of the APA & dV/dt max and prolongation of conduction delay (CD) in toad sciatic neural action potential while it has little effect on APD.Bloocking action of Na+ -channel was measured with the dose required to produce 50% diminution of the value of APA, ie,EC50. EC50 of BTHP was 2.8 folds less than that of lidocaine and 11.9 folds more than that of quinidine, reflecting blocking action of Na+ -channel by BTHP, lidocaine, quinidine respectively.

Protective effects of polarizing cardioplegia with Na~+ channel inhibitor tetrodotoxin (TTX) on isolated rat hearts / 重庆医科大学学报

Objective:To investigate the protective effects of polarizing cardioplegia with Na+ channel inhibitor tetrodotoxin (TTX) on isolated rat hearts.Methods:While Langendorff and Neely perfusion model were steadily established,the rat hearts(10 hearts in each group)were respectively arrested by depolarizing cardioplegia (St.Thomas No.2 solution ,STH-2)in Group Ⅰ(control group),and by polarizing cardioplegia(TTX)in GroupⅡ.These arrested hearts were preserved in corresponding cardioplegia solution respectively at 7℃ for 5 hours and then underwent 30 minute reperfusion.Pre-ischemia and post-ischemia indexes of the rat hearts were studied,including hemodynamic parameters,myocardial enzymology,ATP content,and ultrastructural changes.Results:There were no differences between two groups before myocardial ischemia.But the recovery of myocardial hemodynamic parameters during reperfusoin in GroupⅡwas better than that in GroupⅠ(P