Neural regulation of electrical and mechanical activities in the rat tail artery

Stimulation of the perivascular nerves elicited two types of electrical responses in the rat tail artery—excitatory junction potentials (e.j.p.s) and slow depolarization—and two types of mechanical responses—fast and slow contractions. Fast phasic contractions were triggered whenever action potentials were generated from either the e.j.p. or the slow depolarization reaching threshold. Slow tonic contractions and slow depolarizations were sensitive to -adrenergic blockade. However the slow contraction always preceded the slow depolarization. Bolus doses of exogenous noradrenaline also induced slow contraction and slow depolarization and the development of tension also preceded the membrane potential change. Increasing the external KCl also induced membrane depolarization however, contractions were not observed until the membrane was depolarized positive of –49 mV. In contrast, tension developed readily with membrane potential more negative than –49 mV with exogenous noradrenaline and neural stimulation, suggesting that the action of noradrenaline was not mediated by electromechanical coupling. It was concluded that vascular activity in the rat tail artery could be regulated by the e.j.p., the slow depolarization and also by pharmacomechanical coupling.     

Changes of tension and [Ca2+]i during β-adrenoceptor activation of single,intact fibres from mouse skeletal muscle

-Adrenergic agonists increase tension production in fast-twitch skeletal muscle, but the underlying mechanism is unknown. In the present study we have exposed intact, single fibres from a mouse muscle to the ₂-adrenergic agonist terbutaline. Fibres were stimulated to produce 350-ms tetani at 20–100 Hz while measuring the myoplasmic Ca²⁺ concentration ([Ca²⁺]_i) and tension. The fluorescent indicator Indo-1 was used to measure [Ca²⁺]_i. Application of terbutaline resulted in marked increases of both tetanic [Ca²⁺]_i and tension. Terbutaline had no significant effect on myofibrillar function as judged from normal Ca²⁺ sensitivity and tension production at saturating [Ca²⁺]_i. The rate of [Ca²⁺]_i and tension decline during relaxation was not affected by terbutaline, thus indicating a normal function of the sarcoplasmic reticulum (SR) Ca²⁺ pumps. The effect of terbutaline developed gradually over 5–10 min when fibres were stimulated each minute; the full effect of terbutaline was also obtained after a 10-min rest period in terbutaline. The [Ca²⁺]_i at rest was not affected by terbutaline. In conclusion, -adrenergic stimulation increases tetanic tension by enhancing SR Ca²⁺ release.     

Characterization of the prostanoid receptors and of the contractile effects of prostaglandin F2a in human pial arteries

The contractile and relaxant effects of various prostanoids were studied on isolated human pial arteries. Contractions were elicited with the following order of potency: U46619?U44069>PGB₂>PGF_2a>PGE₂?PGD₂>PGF_1a≥TXB₂, indicating that prostanoid-induced contractions probably are mediated by a thromboxane-sensitive receptor. Relaxation of PGF_2a-contracted arteries was induced with the order of potency: PGE₂> PGE₁>PGD₂?PGD₁. Vessels contrated by K⁺ were relaxed only by PGE,. Since PGI₂ was previously found to be more potent than all the prostanoids tested in the present study, relaxant responses are probably mediated via a PGI₂-sensitive receptor. The roles of free extracellular and cellularly bound calcium for the contractile effects of PGF_2a and K⁺ were estimated by incubating the arteries for various times in calcium-free medium containing 10^-5 M EGTA. Incubation for 5–10 min abolished K⁺-induced contractions, whereas after 40 min of incubation PGF_2a still induced contractions that reached 70% of control. The PGF_2a-induced contraction was biphasic in 8 out of 10 preparations. The second phase could be eliminated by increasing the EGTA-concentration to 10^-4 M, as well as by nifedipine pretreatment. In calcium-free, high K⁺ medium calcium-induced contractions were elicited at lower concentrations in the presence of PGF_2a. The results suggest that PGF_2a-induced contractions in human pial arteries are relatively independent of free extracellular calcium. PGF_2a may promote trans-membrane influx of calcium, as well as release calcium from seemingly superficially located cellular stores.     

Modeling of stimulation–secretion coupling in a chromaffin cell

We constructed a chromaffin cell model for analysis of stimulation–secretion coupling in computer simulation studies. The model includes mechanisms involved in the excitatory synapse, voltage-dependent Na⁺, K⁺ and Ca²⁺ channels, Ca²⁺-activated K⁺ channels (SK type), buffered Ca²⁺ diffusion, Ca²⁺ extrusion, fluorescent Ca²⁺ indicators and Ca²⁺-triggered exocytosis. Calculations of the modeled mechanisms were carried out using the NEURON simulation environment (Hines and Carnevale, Neural Computation 9:1179–1209, 1997). A set of parameter values was determined so as to fit basic experimental results reported in the literature. The model was also applied to simulate our experimental results obtained from chromaffin cells in the perfused rat adrenal medulla. Observed profiles of Ca²⁺responses induced by electrically stimulating the splanchnic nerve with various frequencies (1–50 Hz) were adequately simulated with minor readjustments of parameter values for Ca²⁺influx and extrusion. Secretory responses measured at the same time as the Ca²⁺responses were also simulated with consideration of a time constant to detect catecholamines in the experiment. Similarly, model simulations reproduced both Ca²⁺responses and secretory responses evoked by elevations of the extracellular K⁺ concentration for different periods. The results suggest that the presented model provides a useful tool for analyzing and predicting quantitative relations in various events occurring in stimulation–secretion coupling in chromaffin cells.     

Failure of the rabbit tibial growth plate to respond to the long-term application of a capacitively-coupled electrical field

A continuous 5-V peak-to-peak, 60 kHz capacitively-coupled sine wave signal was applied to the proximal tibial growth plate in fifteen 9-week-old male New Zealand white rabbits for 6 weeks. A pair of flexible stainless steel "injectrodes" was held in place medially and laterally on the surface of the proximal hindlimb in each rabbit by means of tape wrappings. The electrodes were connected to a 9-V battery-operated power unit carried in a dorsal pouch in a body vest worn by each rabbit. Control animals wore the identical apparatus, only the power unit was inactive. Small Tantalum markers were inserted into the anteromedial aspect of the proximal tibial metaphysis 1 cm distal to the proximal tibial growth plate in all of the animals, control and experimental, 2 weeks prior to the onset of electrical stimulation. The distance between the proximal lateral tibial spine and the Tantalum marker, between the Tantalum marker and the apex of the distal tibial intercondylar notch, and between the proximal tibial spine and the distal notch was measured from roentgenograms made at the time of bone marker insertion, at the time of electrode application to the limb, and at the end of the stimulation period. Results indicate that there was no significant difference in tibial lengths between the stimulated and control groups. There was significantly less total body weight gain in both the experimental and control animals than that which occurred in paired normal animals during the same period of time. This failure to thrive may be responsible for the resultant lack of longitudinal growth stimulation of the capacitive coupling.(ABSTRACT TRUNCATED AT 250 WORDS)     

星形胶质细胞-神经元偶联失衡在AD发生进展中的作用及益肾填髓中药的干预机制

星形胶质细胞是中枢神经系统(CNS)重要的神经细胞类型,主要发挥营养与支持作用。星形胶质细胞与神经元之间存在密切的能量与物质偶联关系,能量偶联与物质偶联两者紧密关联、交互为用。近年来大量研究显示,星形胶质细胞-神经元偶联失衡在阿尔茨海默病(AD)的发生与进展中发挥核心作用,星形胶质细胞-神经元偶联网络失衡已成为AD干预的重要靶标并受到日益关注。中医学认为,AD的主要病机是肾虚髓亏,临床常用益肾填髓中药方剂治疗AD取得较好效果。研究发现大量益肾填髓方剂对星形胶质细胞-神经元偶联失衡具有调节和保护作用,中药方剂治疗AD的益肾填髓功效可能与其调节星形胶质细胞-神经元偶联失衡有一定的内在联系。该文就星形胶质细胞-神经元偶联失衡与AD肾虚髓亏病机之间可能内在联系及益肾填精中药干预机制的研究进展做一综述。     

心血管参数对动脉中压力和流量的影响

本文从建立心室-血管优化耦合模型出发,通过求解优化耦合所对应主动脉根部的压力和流量所满足方程,详细讨论动脉中压力和流量随心血管参数的变化规律,所得结果与血液循环系统的生理事实一致。     

Effects of 4-aminopyridine on contractile response and action potential of rabbit papillary muscle

The effects of 4-aminopyridine (4-AP) were studied on isolated papillary muscles from the heart of reserpinized rabbits (at 37°C). The preparations were paced to contract at 0.67 Hz under isometric conditions and the muscle length was adjusted to 95 % of the length for optimum force production. Simultaneous recordings of isometric force and membrane potentials were performed. 4-AP (50 μM) increased peak force by approximately 20% of the control and prolonged the action potential by 20%. Higher concentrations of 4-AP (800 μ.M) resulted in further increments of force and action potential duration (60 and 70% of controls, respectively). Prolongation of the action potential and potentiation of the isometric force was still present one hour after withdrawal of the drug from the perfusate. The results are consistent with the view that 4-AP prolongs the action potential by inhibiting the late repolarizing potassium current. It is suggested that the calcium uptake by the ventricular cell during the prolonged action potential is increased and that this leads to the positive inotropic effect.     

Organ-preference of metastasis

Summary The initial, site-specific colonization of secondary organs by blood-borne cancer cells appears to be mediated by endothelial cell adhesion molecules. These molecules are part of the organ-specific microvascular phenotype and are regulated through complex interactions of the endothelium with the extracellular matrix (e.g., distinct matrix macromolecules and growth factors). They are inducedin vitro by growing unspecific (large vessel) endothelial cells on extracts of organ-specific biomatrices. In many respects, these molecules are similar to the various classes of chemically different adhesion molecules that regulate lymphocyte traffic, but are believed to be distinct from the inducible adhesion molecules that govern leukocyte adhesion during acute episodes of inflammation. Biochemical and biophysical data indicate that preference of tumor cell adhesion to organ-specific microvascular endothelium may not require qualitative differences of such homing receptors between endothelia, but may be explained on the basis of quantitative receptor differences as well as differences of receptor avidity. Following adhesion, the metastatic cascade proceeds by the establishment of metabolic conduits between the endothelium and adherent tumor cells. This heterotypic coupling represents an early step in the extravasation of cancer cells from the microvasculature, initiating endothelial cell retraction from its basement membrane and recanalization around the arrested tumor cell. These events, together with local growth promoting effects exerted by the metastasized organ, are believed to provide the basis for Paget's seed and soil hypothesis of metastasis.     

Hydrophobic Bombyx mori Silk Fibroin: Routes to Functionalization with Alkyl Chains

Bombyx mori silk fibroin (SF) is a very versatile biopolymer due to its biocompatibility and exceptional mechanical properties which make possible its use as a functional material in several applications. SF can be modified with a large variety of chemical approaches which endow the material with tailored chemical–physical properties. Here, a systematic investigation of different routes is reported to graft long alkyl chains on SF based on both liquid- and solid-phase, aiming to modulate its hydrophobic behavior. The liquid phase method involves direct activation of SF tyrosine residues via diazo coupling and cycloaddition reactions, generating hydrophobic materials insoluble in any common solvent. The solid phase approach consists of the chemical modification of drop-casted SF films by esterification of hydroxyl groups of serine, threonine, and tyrosine SF residues with acyl chlorides of fatty acids. For the solid-state functionalization, a new class of hydrophobic pendant groups is synthesized, based on triple esters of gallic acid anhydrides, that are reacted with the biopolymer to further enhance its resulting hydrophobic features.