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Biomedical subjects

Z G Jiang

Publications and source records attributed to Z G Jiang.

At least 19 recordsLinked to original sources

Two resting potential levels regulated by the inward-rectifier potassium channel in the guinea-pig spiral modiolar artery.

1. Intracellular in vitro recordings were made from 771 cells from the spiral modiolar artery (SMA). The initial resting potentials (RPs) displayed a bimodal distribution that was well modelled as a mixture of two Gaussian distributions. About half of the cells had an average RP of -74 mV, and were termed high-RP cells, whereas the other half had an average RP around -41 mV, and were termed low-RP cells. Preparations that were incubated for longer than 24 h contained significantly more high-RP cells than those incubated for less than 8 h. 2. When labelled with the fluorescent dye propidium iodide, 68 and 36 cells were identified as smooth muscle cells (SMC) and endothelial cells (EC), respectively. The RP and input resistance were not significantly different between these two types of cell. Dye coupling was observed only in ECs. Dual cell recordings with 0.2-1.0 mm separation demonstrated the simultaneous existence of high- and low-RP cells and a heterogeneous low-strength electrical coupling. 3. The high-RP cells were depolarized by ACh and by high extracellular potassium concentration (high K(+)). The low-RP cells were usually hyperpolarized by moderately high K(+) (7.5-20 mM) and by ACh. The high K(+)-induced hyperpolarization was suppressed by barium (Ba(2+), 10-50 microM). The putative gap junction blocker 18 beta-glycyrrhetinic acid suppressed the ACh-induced responses in SMCs, but not in ECs. 4. Low-RP cells could rapidly shift the membrane potential to a permanent high-RP state spontaneously or, more often, after a brief application of hyperpolarizing agents including high K(+), ACh, nitric oxide and pinacidil. Once shifted to a high-RP state, the responses of these cells to high K(+) and ACh became similar to those of the original high-RP cells. 5. High-RP cells occasionally shifted their potentials to a low-RP state either spontaneously or after a brief application of 10-50 microM Ba(2+) or 100 microM ouabain. Once shifted to the low-RP state, the response of these cells to high K(+) and ACh became a hyperpolarization. The shift between high- and low-RP states was largely mimicked by wash-in and wash-out of low concentrations of Ba(2+). The shift often showed a regenerative process as a fast phase in its middle course. 6. It is concluded that the cochlear SMA in vitro is composed of poorly and heterogeneously coupled SMCs and ECs, simultaneously resting in one of two distinct states, one a high-RP state and the other a low-RP state. The two RP states are exchangeable mainly due to all-or-none-like conductance changes of the inward-rectifier K(+) channel.

Acetylcholine↗

Glutamate is a mediator of neurotoxicity in secretions of activated HIV-1-infected macrophages.

We sought to identify neurotoxin(s) secreted by HIV-1-infected mononuclear phagocytes that could contribute to the pathophysiology of HIV-1-associated dementia (HAD). Neurotoxic factors were characterized in batches of conditioned media (CM) from human monocyte-derived macrophages (MDM) infected with HIV-1(ADA) and/or activated with lipopolysaccharide (LPS). All of the neurotoxicity was: present in the <3000-Da fraction; blocked by 5 microM MK801; and not trypsin sensitive or extractable into polar organic solvents. Glutamate measured in CM accounted for all neurotoxic effects observed from HIV/LPS CM in astrocyte-poor neuronal cultures and may contribute to the pathophysiology of HIV-1-associated dementia.

AIDS Dementia Complex↗

Pre- and postsynaptic actions of serotonin on rat suprachiasmatic nucleus neurons.

Serotoninergic transmission is implicated in the photic and non-photic regulation of circadian rhythms. 5-HT (1-100 microM), carboxamidotryptamine (5-CT 0.1-10 microM) and (+)-8-hydroxy-dipropylaminotetraline (8-OH-DPAT, 1-30 microM) dose-dependently activated an outward current (5-100 pA) in 30% of neurons voltage-clamped at -60 mV in the suprachiasmatic nucleus (SCN) in vitro slice. EC(50) values were 7.0 microM for 5-HT and 0.2 microM for 5-CT. Serotonin-induced outward current was associated with an increase in input conductance, and the current was blocked by Ba(2+) (1 mM). The amplitude of the current was enhanced by depolarization, reduced by hyperpolarization, and reversed its polarity during a hyperpolarization beyond the potassium equilibrium potential. Mean amplitudes of the 5-HT outward current changed with time of the subjective circadian day. The value near CT2 (23.8 pA) was about 4 times greater than that around CT14 (6.7 pA). Cells that responded with an outward current showed four types of morphology: monopolar, simple bipolar, curly bipolar and radial shaped; they were localized in all parts of the SCN. The EPSC evoked by retino-hypothalamic-tract (RHT) stimulation was inhibited 26% but the inward current induced by exogenously applied glutamate or NMDA was not affected by serotonin agonists. Focal stimulation-induced and spontaneous IPSC but not the exogenous GABA-induced outward current were inhibited by 5-HT agonists in a subpopulation of cells. In conclusion, 5-HT regulates SCN neurons by both pre- and post-synaptic inhibitory mechanisms; the latter may play a key role in modulating SCN circadian rhythm by activation of 5-HT receptors and opening of a potassium channel.

Animals↗

Orphanin-FQ/nociceptin (OFQ/N) modulates the activity of suprachiasmatic nucleus neurons.

Neurons in the suprachiasmatic nucleus (SCN) constitute the principal circadian pacemaker of mammals. In situ hybridization studies revealed expression of orphanin-FQ/nociceptin (OFQ/N) receptor (NOR) mRNA in the SCN, whereas no expression of mRNA for preproOFQ/N (ppOFQ/N) was detected. The presence of OFQ/N peptide in the SCN was demonstrated by radioimmunoassay. SCN neurons (88%) responded dose-dependently to OFQ/N with an outward current (EC50 = 22.3 nM) that was reduced in amplitude by membrane hyperpolarization and reversed polarity near the theoretical potassium equilibrium potential. [Phe1psi(Ch2-NH)Gly2]OFQ/N(1-13)NH2 (3 microM), a putative NOR antagonist, activated a small outward current and significantly reduced the amplitude of the OFQ/N-stimulated current. OFQ/N reduced the NMDA receptor-mediated increase in intracellular Ca2+. When injected unilaterally into the SCN of Syrian hamsters housed in constant darkness, OFQ/N (1-50 pmol) failed to alter the timing of the hamsters' wheel-running activity. However, injection of OFQ/N (0.1-50 pmol) before a brief exposure to light during the midsubjective night significantly attenuated the light-induced phase advances of the activity rhythm. These data are consistent with the interpretation that OFQ/N acting at specific receptors modulates the activity of SCN neurons and, thereby, the response of the circadian clock to light.

Animals↗

Membrane properties and the excitatory junction potentials in smooth muscle cells of cochlear spiral modiolar artery in guinea pigs.

Blood circulation changes in the inner ear play an important role in many physiological and pathological conditions of hearing function. The spiral modiolar artery (SMA) is the terminal artery to the cochlea. It was surrounded with nerve fibers immunostained by an antibody for tyrosine hydroxylase. By using intracellular recording techniques on the acutely isolated SMA, membrane properties of the smooth muscle cells and the neuromuscular transmission in this preparation were investigated. With minimum tension and normal extracellular K(+) concentration (5 mM), the majority of muscle cells showed a resting potential near -80 mV and an input resistance of about 8 MOmega. V/I plot showed an inward rectification in these cells. Barium (50-500 microM) caused strong depolarization and an increase in input resistance. Transmural electrical stimulation evoked stimulation intensity-dependent depolarizations (2-31 mV) following a short latency ( approximately 20 ms). The evoked potential by a low intensity stimulus was completely blocked by 1 microM tetrodotoxin. The potential and a depolarization induced by norepinephrine (10 microM) was usually partially (40-90%) blocked by alpha-receptor antagonists prazosin and/or idazoxan with concentrations up to 1 microM. Action potentials were observed when the depolarization was more than -40 mV. It is concluded that SMA smooth muscle cells, similar to those in other brain small arteries, highly express inward rectifying potassium channels; the cells receive catecholaminergic innervation, and stimulation of the nerves elicited an excitatory junction potential that is partially mediated by adrenergic receptors.

Animals↗

Membrane properties and synaptic inputs of suprachiasmatic nucleus neurons in rat brain slices.

1. Whole-cell recordings were made from 390 neurons of the suprachiasmatic nucleus (SCN) in horizontal brain slices during different portions of the circadian day. The locomotor activity of the rats was measured prior to the preparation of brain slices to insure that each rat was entrained to a 12 h-12 h light-dark cycle. 2. The mean input conductance was 42% higher (1.58 nS) in neurons recorded near the subjective dawn than those (1.11 nS) recorded near the subjective dusk. The current required to hold the neurons at -60 mV also showed a circadian variation with a peak in the middle of the subjective day and a nadir in the middle of the subjective night. Analysis of the variations in the input conductance and the holding current at -60 mV suggested that at least two ion conductances are involved in the pacemaking of the circadian rhythms. 3. Voltage-clamped SCN neurons often had both outward and inward spontaneous postsynaptic currents. The outward currents were blocked by bicuculline but not by strychnine, and were identified as IPSCs mediated by GABAA receptors. The inward currents were blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and were identified as EPSCs mediated by glutamate. Most spontaneous synaptic currents were miniature currents but action potential-dependent large events were seen more often in IPSCs than in EPSCs. 4. Stimulation of the optic nerve or chiasm usually evoked a monosynaptic EPSC which was mediated by both NMDA and non-NMDA receptors. In 13% of cells, optic nerve stimulation evoked an outward current or an inward current followed by an outward current; all the evoked currents were blocked by 4-aminophosphonovaleric acid (APV) and CNQX whereas the outward current only was blocked by bicuculline, suggesting involvement of an inhibitory interneuron. 5. SCN neurons sum the excitatory inputs from both optic nerves; on average each SCN cell receives innervation from at least 4.8 retinohypothalamic tract (RHT) axons. 6. Focal stimulation in the vicinity of the recorded neuron revealed that nearly all SCN neurons receive local or extranuclear GABAergic inputs operating via GABAA receptors. The EPSCs activated by such stimulation were not significantly different in amplitude and pharmacological properties from those induced by RHT stimulation. 7. One hundred and one neurons were labelled with neurobiotin during whole-cell recording. Based on the dendritic structures, four types of SCN neurons (monopolar, radial, simple bipolar and curly bipolar) were identified. The curly bipolar cells had a higher membrane conductance, holding current and hyperpolarization-activated current (Ih) amplitude than the other neuronal types. Radial neurons did not respond to optic nerve stimulation, which activated EPSCs in the other cell types.

Animals↗

Tracer and electrical coupling of rat suprachiasmatic nucleus neurons.

Whole-cell recording from single neurons of the suprachiasmatic nucleus with an electrode containing the tracer neurobiotin resulted in the staining of multiple neurons in 30% of the cases. Typically, one neuron was darkly stained with dendritic processes and an axon clearly visible while other neurons were lightly stained. The darkly-stained cells were identified as the recorded neuron and tracer-coupled to one to five lightly stained neurons. The resting membrane potential, input membrane conductance, membrane capacitance, the decay time constant and the maximum H-current amplitude of the recorded neurons with tracer-coupled cells were not significantly different from those of neurons not showing tracer coupling. Stimulation of the preoptic area activated an antidromic action potential or an all-or-none small slow inward current in some neurons when the synaptic transmission was blocked by a calcium-free/Mn2+ solution. The small slow inward current did not "collide" with an orthodromically activated action spike suggesting that the current represents the signal from an electrotonically-coupled neuron. In addition, the frequency of biphasic field currents from a neighbouring cell firing were increased by depolarization and decreased by hyperpolarization of the recorded cell. These data demonstrate a chemical and electrical low-resistance coupling of suprachiasmatic nucleus neurons, which could be important in synthesizing the suprachiasmatic nucleus circadian rhythm.

Animals↗

Regulation by nerve growth factor of neuropeptide phenotypes in primary cultured sensory neurons prepared from aged as well as adult mice.

The present study investigated neuropeptide phenotypes of aged, as well as adult, mouse sensory neurons. Proportions of somatostatin (SOM), calcitonin gene related protein (CGRP) and neuropeptide Y (NPY) immunoreactive (ir)-neurons were lower in primary cultures from aged (2 years) mice than in those from adult (6 months) animals, but similar for substance P (SP) in the absence of exogenous nerve growth factor (NGF). Addition of NGF, significantly enhanced (P < 0.05) proportions of SP, NPY and CGRP ir-neurons in both adult and aged cultures, whereas SOM ir-neurons were not affected in either. Thus SP, CGRP, NPY and SOM phenotypes are retained in cultured aged DRG neurons and some phenotypes can remain sensitive to NGF regulation.

Aging↗

Melatonin activates an outward current and inhibits Ih in rat suprachiasmatic nucleus neurons.

Whole-cell voltage-clamp recordings were made from suprachiasmatic nucleus (SCN) neurons maintained in horizontal brain slices. The majority of neurons exhibited spontaneous and evoked excitatory and inhibitory synaptic currents (EPSC and IPSC), mediated by glutamate and GABA respectively. Melatonin had no effect on either the spontaneous or evoked EPSC or IPSC. Application of melatonin (0.1-30 microM) during circadian time (CT) 9-12 activated an outward current at -60 mV and increased the membrane conductance in a concentration-dependent manner. The current was augmented by depolarization, reduced by hyperpolarization and, in some cells, reversed its polarity near the potassium equilibrium potential. Some neurons also responded to melatonin during other times of the circadian day (CT 3-9 or CT 12-15). Hyperpolarizing steps, in a portion of cells, activated an inward cation current which resembled the Ih described in other neurons. Melatonin (10 microM) inhibited activation of the Ih. These data indicate that melatonin may inhibit SCN neurons by activating a potassium current and inhibiting the Ih.

Animals↗

The effects of nerve growth factor on neurite outgrowth from cultured adult and aged mouse sensory neurons.

The present study demonstrated, by detailed computer image analysis, that cultured aged (2 years) as well as adult (6 months) mouse sensory neurons retained a capacity for neurite extension throughout the 9-day period investigated. Neurites arose predominantly from intermediate- and large-sized neurons. The numbers of neurites, the neurite with the major or longest length, the number of branches and the total extent of neuritogenesis were measured blindly from a total of 440 adult and 451 aged neurons, in five independent experiments for each, and data were statistically tested by ANOVA. The results demonstrated that NGF significantly enhanced neurite outgrowth from aged neurons in a low density enriched culture system as well as from adult neurons, and thereby extends the previous findings from other laboratories [7,25], which only monitored the response of young adult neurons. For total neurite lengths of adult and aged neurons differences were evident by the end of the 9-day culture period: major neurite length enhancement was predominantly responsible for the effect on adult neurons, whereas increased branch lengths contributed more in the case of aged neurons.

Age Factors↗

Presynaptic inhibition by baclofen of retinohypothalamic excitatory synaptic transmission in rat suprachiasmatic nucleus.

Optic nerve stimulation evoked monosynaptic excitatory postsynaptic currents in suprachiasmatic nucleus neurons maintained in vitro. These currents were completely blocked by a combination of glutamate receptor antagonists, 6-cyano-7-nitroquinoxaline-2,3-dione and 4-aminophosphonovaleric acid. Stimulation of the ipsilateral or contralateral suprachiasmatic nucleus produced a biphasic response consisting of an excitatory postsynaptic current followed by an bicuculline-sensitive inhibitory postsynaptic current. Most suprachiasmatic nucleus neurons had spontaneous inhibitory and excitatory synaptic currents produced by action potential-independent and, less frequently, action potential-dependent release of GABA and glutamate. Baclofen reversibly reduced the amplitude of excitatory postsynaptic currents evoked by optic nerve stimulation and the effect was antagonized by 2-hydroxysaclofen. In addition, baclofen reduced the frequency but not the amplitude of the spontaneous miniature excitatory postsynaptic currents. In a subset of suprachiasmatic nucleus neurons, baclofen induced an outward current, probably by increasing a potassium conductance. Baclofen had no effect on either evoked or spontaneous inhibitory postsynaptic currents or on currents activated by pulse application of glutamate. These data indicate that activation of GABAB receptors can inhibit suprachiasmatic nucleus neurons by two mechanisms. The first is to inhibit the release of glutamate from terminals of the retinohypothalamic tract. The second is the postsynaptic activation of a potassium conductance in a portion of these neurons.

2-Amino-5-phosphonovalerate↗

[The exciting origin of guinea-pig inferior mesenteric ganglion neurons in vivo].

Intracellular recording in vivo showed that spontaneous activities of guinea-pig inferior mesenteric ganglion (IMG) neurons were inhibited when any one of the four groups of the nerves connected to the IMG was cutted or blocked, indicating that all the four groups of nerves sent in excitatory input. Colonic and hypogastric nerves convey the peripheral excitation respectively from colon and bladder. Intermesenteric nerve sends in peripheral excitatory input from colon and central from spinal cord. This finding suggests that the excitation of the prevertebral ganglia originates from not only spinal cord as claimed tranditionally, but also the peripheral organs. The latter exits stronger effect than the former. It seems that IMG is an integration neurocenter rather than a simple signal relay station from the central nervous system to peripheral effectors.

Animals↗

Actions of 5-hydroxytryptamine on ventral tegmental area neurons of the rat in vitro.

Intracellular recordings were made with conventional microelectrodes and with whole-cell patch-clamp electrodes from neurons of the rat ventral tegmental area and substantia nigra zona compacta in vitro. Neurons were distinguished as principal cells and secondary cells; it is known from previous work that most principal cells contain dopamine whereas secondary cells do not. 5-Hydroxytryptamine (5-HT; 3-100 microM) depolarized (or evoked an inward current at -60 mV) 46% of 153 principal cells; a small proportion (11%) of cells were hyperpolarized (or showed outward current at -60 mV). Secondary cells were equally likely to be depolarized (or inward current at -60 mV, 30% of 80 cells) or hyperpolarized (or outward current at -60 mV, 28%). approximately 40% of each type of cell were unaffected by 5-HT. Depolarizing responses of 5-HT were mimicked by (+/-)-1-(2,5-dimethoxy-4-iodophenyl)- 2-aminopropane (DOI) and blocked by ketanserin. Hyperpolarizing responses were mimicked by dipropyl-5-carboxamidotryptamine and reversed polarity at the K+ equilibrium potential. Inhibitory postsynaptic potentials (or currents) mediated at GABAA receptors occurred spontaneously in some principal cells; they were reversibly blocked by tetrodotoxin and bicuculline. 5-HT either increased or decreased the frequency of these synaptic potentials but did not change their mean amplitude or decay time.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphetamines↗

Neurotensin excitation of rat ventral tegmental neurones.

1. Whole-cell patch-clamp recordings were made from ventral tegmental area neurones in rat midbrain slices in vitro. In principal cells, which are presumed to contain dopamine, neurotensin (< or = 1 microM) caused an inward current at -60 mV in thirty of forty-seven neurones and had no effect on the remainder. In secondary neurones, neurotensin caused an inward current in twelve of thirty-three cells. 2. The inward current evoked by neurotensin reached a maximum amplitude of about 80 pA, and declined over several minutes when the application was discontinued. The current was most commonly accompanied by a decrease in membrane conductance and reversed polarity at a strongly hyperpolarized potential; this reversal potential was less negative in a higher extracellular potassium concentration. Neurotensin also caused an inward current even in potassium-free internal and external solutions; this current was accompanied by a conductance increase, reversed close to 0 mV and was inhibited by reduction of the extracellular sodium concentration (from 150 to 20 mM). 3. The inward current was associated with a large increase in noise; this persisted in calcium-free solutions but was inhibited by low sodium concentration. The increase in noise was more prominent at hyperpolarized potentials. The amplitude of the unitary current underlying the increase in noise was estimated from the ratio of the variance to the mean as about 1.5 pA at -100 mV. 4. When the recording was made with an electrode containing guanosine 5'-thio-triphosphate, the steady inward current evoked by neurotensin did not reverse when the application was discontinued. When the recording electrode contained pertussis toxin, the action of neurotensin was not different although outward currents evoked by dopamine and baclofen declined with time. 5. It is concluded that neurotensin excites ventral tegmental area neurones by activating a pertussis toxin-insensitive guanosine nucleotide-binding protein. This leads to a reduction in membrane potassium conductance and an increase in membrane sodium conductance, the relative contribution of which varies from cell to cell.

Amino Acid Sequence↗

Platelet-activating factor inhibits excitatory transmission in rat neostriatum.

Platelet-activating factor (PAF) and its receptor have been found in mammalian brain but its neuronal action is unclear. Using brain slice and whole-cell patch-clamp techniques, it was found that PAF dose-dependently inhibited excitatory postsynaptic current in neostriatal neurons but not the current induced by exogenously applied glutamate. These effects were also observed with the synthetic agonist 2-methylcarbamyl-PAF and were blocked by BN50739, a competitive antagonist at PAF receptors. It is concluded that PAF acts presynaptically to inhibit the release of glutamate at excitatory synapses in the neostriatum.

2-Amino-5-phosphonovalerate↗

Effects of nerve growth factor on the survival of primary cultured adult and aged mouse sensory neurons.

This study investigated the effects of exogenous nerve growth factor (NGF) on the survival and differentiation in primary culture of sensory neurons isolated from adult (6 months) and aged (2 years) mice. For neurons prepared from adult mice, a concentration effect was evident during a 2 week culture period: Neuronal counts in cultures supplemented with 25 and 50 ng/ml NGF did not differ significantly from those of control cultures without exogenous NGF or those with anti-NGF included in the culture medium, whereas cultures supplemented with either 100 or 200 ng/ml NGF contained higher numbers of neurons throughout the culture period. Cultures prepared from aged mice contained less neurons than those from adult mice, although those supplemented with 100 ng/ml NGF retained higher neuronal numbers than cultures from aged mice which did not receive exogenous NGF. Neuronal diameters were measured to investigate whether specific subpopulations of neurons were more dependent on NGF; the results indicate that neurons of a medium-larger diameter were more prevalent than cells with a smaller diameter following NGF administration. A shape index was calculated for each culture regimen; with longer culture periods a higher proportion of spindle-shaped neurons was observed.

Aging↗

Dopamine and baclofen inhibit the hyperpolarization-activated cation current in rat ventral tegmental neurones.

1. Whole-cell patch-clamp recordings were made from dopamine-containing ventral tegmental area neurones in slices of rat midbrain. An inward current (Ih) was activated by hyperpolarization from -60 mV. 2. Dopamine (30 microM) reduced the amplitude of Ih by 10-30% at potentials from -70 to -120 mV. The effect was concentration dependent, mimicked by the D2 agonist quinpirole, and prevented by the D2 antagonist (-)-sulpiride. Baclofen (0.3-3 microM) also inhibited Ih; this action was antagonized by 2-hydroxysaclofen but not by (-)-sulpiride. The decrease in Ih resulted from a reduction in the maximal current with no change in the voltage dependence. 3. The action of dopamine was unaffected by cadmium (200 microM), forskolin (10 microM), the adenylyl cyclase inhibitor 2',3'-dideoxyadenosine (100 microM), or by intracellular solution containing cyclic AMP (2 mM). 4. Ih was progressively reduced during the first 5-10 min of recording with electrodes containing guanosine 5'-O-(3-thiotriphosphate); after this time, dopamine had no further effect. 5. It is concluded that agonists acting at D2 receptors and GABAB receptors reduce Ih in ventral tegmental neurones.

Action Potentials↗