Mechanisms of afterhyperpolarization in lobster olfactory receptor neurons

In lobster olfactory receptor neurons (ORNs), depolarizing responses to odorants and current injection are accompanied by the development of an afterhyperpolarization (AHP) that likely contributes to spike-frequency adaptation and that persists for several seconds after termination of the response. A portion of the AHP can be blocked by extracellular application of 5 mM CsCl. At this concentration, CsCl specifically blocks the hyperpolarization-activated cation current (Ih) in lobster ORNs. This current is likely to be active at rest, where it provides a constant, depolarizing influence. Further depolarization deactivates Ih, thus allowing the cell to be briefly hyperpolarized when that depolarizing influence is removed, thus generating an AHP. Reactivation of Ih would terminate the AHP. The component of the AHP that could not be blocked by Cs+ (the Cs(+)-insensitive AHP) was accompanied by decreased input resistance, suggesting that this component is generated by increased conductance to an ion with an equilibrium potential more negative than the resting potential. The Cs(+)-insensitive AHP in current clamp and the underlying current in voltage clamp displayed a reversal potential of approximately -75 mV. Both EK and ECl are predicted to be in this range. Similar results were obtained with the use of a high Cl- pipette solution, although that shifted ECl from -72 mV to -13 mV. However, when EK was shifted to more positive or negative values, the reversal potential also shifted accordingly. A role for the Ca(2+)-mediated K+ current in generating the Cs(+)-independent AHP was explored by testing cells in current and voltage clamp while blocking IK(Ca) with Cs+/Co(2+)-saline. In some cells, the Cs(+)-independent AHP and its underlying current could be completely and reversibly blocked by Cs+/Co2+ saline, whereas in other cells some fraction of it remained. This indicates that the Cs(+)-independent AHP results from two K+ currents, one that requires an influx of extracellular Ca2+ and one that does not. Collectively, these findings indicate that AHPs result from three phenomena that occur when lobster ORNs are depolarized: 1) inactivation of the hyperpolarization-activated cation current, 2) activation of a Ca(2+)-mediated K+ current, and 3) activation of a K+ current that does not require influx of extracellular Ca2+. Roles of these processes in modulating the output of lobster ORNs are discussed.     

A novel stretch receptor in the jaw of the rat

We report here an unusual type of stretch receptor found on each side of the rat jaw. This receptor has unique morphological features: it is quite long (24-28 mm), lies in connective tissue in between masticatory muscles, and extends between the medial pterygoid muscle-tendon on the maxilla and the masseter-tendon on the mandible through a zigzag course, forming a Greek capital letter sigma when viewed from the side. The receptor is neither in parallel nor in series with any masticatory muscles and receives multiple innervation. The receptor increases its length when the jaw closes and shortens when the jaw opens. Electron microscopy revealed axial structures composed of a central cellular core surrounded by tightly packed collagen bundles which are separated from the capsule by a wide capsular space. Most of the sensory endings are found among axial collagen bundles, some in between core cells. The core cells have many finger-like processes on their surface, being coupled by desmosomes. The origin and nature of these cells are unclear. The wide capsular space is filled with Alcian blue positive substrate, probably acid glycosaminoglycans. The structures of outer and inner capsules are similar to those of muscle spindles, the former being composed of three to ten layers of thin flattened cells. The response of the receptor was examined with in vivo as well as in vitro preparations. In in vivo experiments, impulse discharges from this receptor increased with the increase in jaw closing. When the jaw was fully opened the impulse discharge from this receptor disappeared.(ABSTRACT TRUNCATED AT 250 WORDS)     

Action potential and sodium current in the slowly and rapidly adapting stretch receptor neurons of the crayfish (Astacus astacus)

Action potentials (APs) and sodium current from the slowly and the rapidly adapting stretch receptor neurons in the crayfish (Astacus astacus) were recorded with a two microelectrode voltage- and current-clamp technique. In the rapidly adapting neuron the APs had a duration of 3.2 +/- 0.2 ms (means +/- SE) and an amplitude of 55.2 +/- 1.5 mV. In the slowly adapting receptor neuron APs had a duration of 4.1 +/- 0.2 ms and an amplitude 79.9 +/- 2.0 mV. APs in the rapidly adapting neuron had a larger amplitude if they were recorded from the axon. In the rapidly adapting neuron adaptation of the impulse response was prolonged by hyperpolarization or by exposure to scorpion venom. Also, sinusoidal current stimulation added to the current steps prevented impulse adaptation. Block of the potassium currents in the slowly adapting neuron resulted in a rapid adaptation of the impulse response. The maximum sodium current amplitude was 313 +/- 15 nA in slowly adapting neuron and 267 +/- 11 nA in the rapidly adapting neuron. The current-voltage relationship showed a hump most marked in the slowly adapting neuron and abolished when a depolarizing prepulse was given. In the rapidly adapting neuron the inactivation starts at a more negative potential (Eh = -45 mV) and is faster compared with the slowly adapting neuron (Eh = -41 mV). The crude scorpion venom of Leiurus quinquestriatus (ScVLq) shifted hinfinity curve toward more positive potentials and slowed down the rate of inactivation. The results indicate the possible presence of more than one Na+ channel population and that the relative density and the spatial distribution is different in the slowly and rapidly adapting neuron. The difference contributes to the adaptive properties of the two receptor neurons.     

Transduction properties of tracheal stretch receptors

1. Using single fibre vagal afferent recording, we have studied the behavior of slowly adapting stretch receptors located in an isolated, in situ, segment of the trachea in dogs. Responses to positive and negative steady and oscillating transmural pressures were investigated. 2. Seventy-eight per cent of the receptors studied were tonically active at resting tracheal volume. Ninety per cent showed a more pronounced response to positive than to negative transmural pressures. 3. During pressure oscillations the majority of the receptors had a higher discharge frequency at any given pressure during the ascending phase of the pressure wave than at the same pressure under static conditions. During most of the ensuing descent of pressure toward zero the discharge frequency led transmural pressure. 4. With increasing frequency of oscillation the differences from the static responses increased (dP/dt sensitivity), especially during the ascending limb of the pressure oscillation (rectifying behavior). 5. In a small number of receptors, discharge frequency lagged behind transmural pressure or was in phase with it ("no loop" pattern). 6. In three cases the same receptor exhibited dP/dt sensitivity during positive pressure oscillations, whereas discharge frequency lagged behind pressure during negative pressure oscillations. This indicates that the lack of dP/dt sensitivity exhibited under negative pressure conditions does not represent an intrinsic property of these receptors, but reflects some aspect of their mechanical arrangement within the airway wall. 7. THESE PATTERNS OF RESPONSE ARE DISCUSSed in terms of intrinsic and extrinsic characteristics of the receptors. 8. The physiological implications of stretch receptor behaviour are also considered.     

Sodium-gated cation channel implicated in the activation of lobster olfactory receptor neurons

The role of Na+-activated channels in cellular function, if any, is still elusive. We have attempted to implicate a Na+-activated nonselective cation channel in the activation of lobster olfactory receptor neurons. We show that a Na+-activated channel occurs in the odor-detecting outer dendrites. With the use of pharmacological blockers of the channel together with ion substitution, we show that a substantial part of the odor-evoked depolarization in these cells can be ascribed to a Na+-activated conductance. We hypothesize, therefore, that the Na+-activated channel amplifies the receptor current as a result of being secondarily activated by the primary odor transduction pathway.     

张力减径机电流,转速监测系统

针对宝钢钢管厂张力减径机在生产中的问题，研制了在线监测减径机电流和转速微机系统，本文介绍系统的工作原理、性能、结构及其在应用中取得的满意效果。     

Na/K pump current in guinea pig cardiac myocytes and the effect of Na leak

INTRODUCTION: Steady-state Na/K pump current (Ip) in adult guinea pig ventricular myocytes was studied to determine the effect on the Na/K pump of transmembrane Na leak, membrane potential, and pipette Na concentration. METHODS AND RESULTS: Using conventional whole cell, patch clamp techniques, Ip was identified as either Ko-sensitive or ouabain-sensitive current when most other membrane currents were inhibited. Control experiments showed that there were no Ko-sensitive currents other than Ip under the conditions of our experiments. Ip was found to be similar to that reported by others being voltage dependent between -130 and 0 mV and having a half maximal activation by Nai of 28 mM. Ouabain sensitivity was also measured, and it was found that there were two binding sites with the high affinity site comprising 5% to 10% of the total and having an apparent affinity 1000-fold higher than the low affinity site. Apparent affinity of both sites was shifted about 10-fold (higher affinity) by increasing Nai from 10 to 85 mM. When internally perfused with 0 Na solution, Na leak through the membrane was found to be linearly related to Na/K pump activity. In contrast to prior suggestions, Ip was not correlated with series resistance when there was a large transmembrane Na gradient. CONCLUSION: These data suggest that, under conditions of high transmembrane Na gradient, Na leak through the membrane plays a significant role in determining Na/K pump activity.     

张力减径机集中差速传动系统分析

张力减径机的主传动系统是由集中差速传动系统和单独传动系统组成的混合传动系统，本文简析了主传动系统的结构特点，并对其集中差速传动系统的传动机构进行了详尽的分析，从而对同类引进设备的国产化具有重要的实际意义。     

Passive properties of human skeletal muscle during stretch maneuvers. A review

Despite limited scientific knowledge, stretching of human skeletal muscle to improve flexibility is a widespread practice among athletes. This article reviews recent findings regarding passive properties of the hamstring muscle group during stretch based on a model that was developed which could synchronously and continuously measure passive hamstring resistance and electromyographic activity, while the velocity and angle of stretch was controlled. Resistance to stretch was defined as passive torque (Nm) offered by the hamstring muscle group during passive knee extension using an isokinetic dynamometer with a modified thigh pad. To simulate a clinical static stretch, the knee was passively extended to a pre-determined final position (0.0875 rad/s, dynamic phase) where it remained stationary for 90 s (static phase). Alternatively, the knee was extended to the point of discomfort (stretch tolerance). From the torque-angle curve of the dynamic phase of the static stretch, and in the stretch tolerance protocol, passive energy and stiffness were calculated. Torque decline in the static phase was considered to represent viscoelastic stress relaxation. Using the model, studies were conducted which demonstrated that a single static stretch resulted in a 30% viscoelastic stress relaxation. With repeated stretches muscle stiffness declined, but returned to baseline values within 1 h. Long-term stretching (3 weeks) increased joint range of motion as a result of a change in stretch tolerance rather than in the passive properties. Strength training resulted in increased muscle stiffness, which was unaffected by daily stretching. The effectiveness of different stretching techniques was attributed to a change in stretch tolerance rather than passive properties. Inflexible and older subjects have increased muscle stiffness, but a lower stretch tolerance compared to subjects with normal flexibility and younger subjects, respectively. Although far from all questions regarding the passive properties of humans skeletal muscle have been answered in these studies, the measurement technique permitted some initial important examinations of vicoelastic behavior of human skeletal muscle.     

Molecular cloning of a lobster Gbeta subunit and Gbeta expression in olfactory receptor neuron dendrites and brain neuropil

BACKGROUND: Basic fibroblast growth factor (bFGF) promotes angiogenesis and healing of gastric ulcers in rats, and bFGF expression is up regulated in such ulcers. However, little is known about expression of bFGF in human gastric mucosa. AIMS: To investigate bFGF expression in intact human gastric mucosa and gastric ulcers and to determine whether low bFGF content or altered binding by mucosa is associated with ulceration. SUBJECTS: Endoscopy outpatients, gastrectomy patients, and organ donors. METHODS: bFGF was isolated by heparin affinity chromatography and characterised by western blotting and endothelial cell bioassay. bFGF was measured by immunoassay and its distribution defined by immunohistochemistry and in situ hybridisation. Binding of bFGF by heparan sulphate proteoglycans was investigated by sodium chloride and heparin extraction. RESULTS: Bioactive bFGF (19 kDa) was detected in normal mucosa but bFGF mRNA was not found. bFGF expression was up regulated in granulation tissue endothelial cells, mononuclear cells, and epithelial cells at the ulcer rim. Gastric ulcer patients had constitutively low bFGF concentrations in intact antral mucosa which were not explained by changes in binding to heparan sulphate proteoglycans. CONCLUSIONS: bFGF expression is up regulated in human gastric ulcers. Low intact mucosal bFGF content is associated with gastric ulceration.     

Muscarinic receptor subtypes controlling the cationic current in guinea-pig ileal smooth muscle

1. The effects of muscarinic antagonists on cationic current evoked by activating muscarinic receptors with the stable agonist carbachol were studied by use of patch-clamp recording techniques in guinea-pig single ileal smooth muscle cells. 2. Ascending concentrations of carbachol (3-300 microM) activated the cationic conductance in a concentration-dependent manner with conductance at a maximally effective carbachol concentration (Gmax) of 27.4+/-1.4 nS and a mean -log EC50 of 5.12+/-0.03 (mean+/-s.e.mean) (n=114). 3. Muscarinic antagonists with higher affinity for the M2 receptor, methoctramine, himbacine and tripitramine, produced a parallel shift of the carbachol concentration-effect curve to the right in a concentration-dependent manner with pA2 values of 8.1, 8.0 and 9.1, respectively. 4. All M3 selective muscarinic antagonists tested, 4-DAMP, p-F-HHSiD and zamifenacin, reduced the maximal response in a concentration-dependent and non-competitive manner. This effect could be observed even at concentrations which did not produce any increase in the EC50 for carbachol. At higher concentrations M3 antagonists shifted the agonist curve to the right, increasing the EC50, and depressed the maximum conductance response. Atropine, a non-selective antagonist, produced both reduction in Gmax (M3 effect) and significant increase in the EC50 (M2 effect) in the same concentration range. 5. The depression of the conductance by 4-DAMP, zamifenacin and atropine could not be explained by channel block as cationic current evoked by adding GTPgammaS to the pipette (without application of carbachol) was unaffected. 6. The results support the hypothesis that carbachol activates M2 muscarinic receptors so initiating the opening of cationic channels which cause depolarization; this effect is potentiated by an unknown mechanism when carbachol activates M3 receptors. As an increasing fraction of M3 receptors are blocked by an antagonist, the effects on cationic current of an increasing proportion of activated M2 receptors are disabled.     

Mechanical stretch induces hypertrophic responses in cardiac myocytes of angiotensin II type 1a receptor knockout mice

Many lines of evidence have suggested that angiotensin II (AngII) plays an important role in the development of cardiac hypertrophy through AngII type 1 receptor (AT1). To determine whether AngII is indispensable for the development of mechanical stress-induced cardiac hypertrophy, we examined the activity of mitogen-activated protein kinase (MAPK) family and the expression of the c-fos gene as hypertrophic responses after stretching cultured cardiac myocytes of AT1a knockout (KO) mice. When cardiac myocytes were stretched by 20% for 10 min, extracellular signal-regulated protein kinases (ERKs) were strongly activated in KO cardiomyocytes as well as wild type (WT) myocytes. Both basal and stimulated levels of ERKs were higher in cardiomyocytes of KO mice than in those of WT mice. Activation of another member of the MAPK family, p38(MAPK), and expression of the c-fos gene were also induced by stretching cardiac myocytes of both types of mice. An AT1 antagonist attenuated stretch-induced activation of ERKs in WT cardiomyocytes but not in KO cardiomyocytes. Down-regulation of protein kinase C inhibited stretch-induced ERK activation in WT cardiomyocytes, whereas a broad spectrum tyrosine kinase inhibitor (genistein) and selective inhibitors of epidermal growth factor receptor (tyrphostin, AG1478, and B42) suppressed stretch-induced activation of ERKs in KO cardiac myocytes. Epidermal growth factor receptor was phosphorylated at tyrosine residues by stretching cardiac myocytes of KO mice. These results suggest that mechanical stretch could evoke hypertrophic responses in cardiac myocytes that lack the AT1 signaling pathway possibly through tyrosine kinase activation.     

The effects of serial stretch loading on stretch work and stretch-shorten cycle performance in the knee musculature

Diabetes mellitus is associated with an inordinately high risk of virtually all manifestations of cardiovascular-renal disease including atherosclerotic coronary and peripheral vascular disease, congestive heart failure, stroke, nephropathy, and cardiomyopathy unassociated with coronary heart disease. Abnormalities in the renin-angiotensin-aldosterone-kinin (RAAK) cascade have been implicated in the pathogenesis and clinical expression of these cardiovascular-renal sequelae. Thus, pharmacological modulation of the RAAK system is an attractive therapeutic target in diabetes mellitus. Indeed, emerging data from human clinical studies appear to confirm this thesis.     

Methanethiosulfonate derivatives inhibit current through the ryanodine receptor/channel

To identify regions of the ryanodine receptor (RyR) important for ion conduction we modified the channel with sulfhydryl-reacting compounds. After addition of methanethiosulfonate (MTS) compounds channel conductance was decreased while other channel properties, including channel regulation by ATP, caffeine, or Ca, were unaffected. The site of action was accessible to the MTS compounds from the cytoplasmic, but not the luminal, side of the channel. In addition, the hydrophilic MTS compounds were only effective when the channel was open, suggesting that the compounds covalently modify the channel from within the water-filled ion conducting pathway. The decrease in channel current amplitude occurred in a step-wise fashion and was irreversible and cumulative over time, eventually leading to the complete block of channel current. However, the time required for each consecutive modification during continuous exposure to the MTS compounds increased, suggesting that successive modification by the MTS compounds is not independent. These results are consistent with the hypothesis that the channel forms a wide vestibule on the cytoplasmic side and contains a much smaller opening on the luminal side. Furthermore, our results indicate that the MTS compounds can serve as functional markers for specific residues of the RyR to be identified in molecular studies.     

我国高炉结构现状分析

1 概述 2000年我国生铁产量为1.31亿t,比1999年增加0.11亿t,其中重点企业产铁1.10亿t,比1999年增加0.08亿t,其他企业产铁0.20亿t,比1999年增加0.027亿t。 近年来,我国生铁产量一直处于高速增长阶段,这与我国钢产量一直处于高速增长     

Dopaminergic modulation of inhibitory glutamate receptors in the lobster stomatogastric ganglion

The intrinsic rhythmicity of the spiny lobster stomatogastric ganglion (STG) is strongly influenced by the strengths of the graded synapses between identified cells within the neural network. These synaptic strengths can be powerfully influenced by chemical neuromodulators such as dopamine and serotonin. Most of the intraganglionic chemical synapses in the STG are mediated by postsynaptic inhibitory glutamate receptors (IGluRs). To determine whether or not direct effects on these IGluRs contribute to the modulation of synaptic strength, unidentified STG neurons were extracted into primary culture and the effects of these aminergic neuromodulators on the glutamate-evoked membrane current were assessed. Dopamine (100 microM) reliably and significantly reduced the whole cell slope conductance of all IGluRs tested. Serotonin (20 microM) never affected the IGlu response, although it clearly altered other cellular membrane properties. Although all identified STG neurons may not conform to these observations, the data reveal a specific dopamine-activated modulatory pathway within cultured neurons that reduces IGluR slope conductance. The relationship between IGluR modulation and net synaptic modulation in situ contributes to an emerging model in which synaptic strengths can be multiply modulated at different functional sites, yielding a complex, distributed, and state-dependent regulatory structure.     

Calcium mediates the activation of the inhibitory current induced by odorants in toad olfactory receptor neurons

In toad olfactory neurons, a putrid odorant mixture inducing inhibitory responses increases Ca2+-activated K+ conductance, developing a hyperpolarizing receptor potential. Removal of extracellular Ca2+ or exposure to nifedipine reversibly reduced the inhibitory response, suggesting that odorants induce a Ca2+ influx. We show evidence for an odorant-induced Ca2+ current. Using confocal microscopy, it is shown that odorants induce a nifedipine-sensitive elevation of Ca2+ in the apical end of the cell. These results suggest an inhibitory mechanism in which an apical Ca2+ influx causes an increase in internal Ca2+, opening Ca2+-activated K2+ channels that lead to membrane hyperpolarization.     

Serotonin inhibits calcium-activated K+ current in rat taste receptor cells

Little is definitively known of the identity or actions of neurotransmitters utilized within mammalian taste buds. Serotonin has been immunocytochemically localized to taste cells of several species but its physiological actions are unknown. Using whole-cell patch clamp recordings on dissociated posterior rat taste cells, data are presented to suggest that exogenously applied serotonin inhibits a calcium-activated potassium current by up to 50%. This current, best visualized at depolarized holding potentials, is both apamin- and charybdotoxin-sensitive. Approximately 60% of the tested taste cells were serotonin sensitive. This inhibition was mimicked by N-(3-trifluoromethylphenyl)piperazine (TFMPP), a general serotonin receptor agonist, by 8-hydroxy-dipropylaminotetralin (8-OH-DPAT), a selective 5-HT1A receptor agonist, but not by phenylbiguanide, a 5-HT3 receptor agonist. These are the first data to establish a physiological effect of serotonin on mammalian taste cells.