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The detection of differential beta-adrenoceptor blockade in the cat.

1. Tachycardia and bronchodilatation were produced by intravenous dimethylphenylpiperazinium iodide (DMPP) in the spinal or pithed cat. Responses other than those involving beta-adrenoceptors were minimized by appropriate blocking agents.2. With intact adrenals, both the tachycardia and bronchodilatation with 10 mug/kg DMPP were equal to those with 1 mug/kg adrenaline.3. After adrenalectomy, tachycardia with 100 mug/kg DMPP was equal to that with 1.5 mug/kg adrenaline, but the bronchodilatation was equal to that with only 0.3 mug/kg. This difference may reflect the relative activity of the sympathetic supply to the organs.4. After adrenalectomy, propranolol was 3 times as effective against bronchodilatation due to DMPP as against tachycardia. Practolol was inactive against bronchodilatation.5. With intact adrenals, propranolol reduced both tachycardia and bronchodilatation due to DMPP equally. Propranolol also antagonized equally both effects of adrenaline in the pithed cat after adrenalectomy.6. In the spinal cat, propranolol caused bradycardia and bronchoconstriction that persisted after adrenalectomy or pithing. It was reduced by pempidine and guanethidine and is attributed to spontaneous adrenergic neuronal activity.7. The Appendix describes a device for cycle-by-cycle spirometry and correction for zero drift of a micromanometer, used in this study for the continuous recording of bronchial resistance.

Adrenalectomy↗

Effects of lithium ions on electrical activity in sympathetic ganglia of the bullfrog.

1 The mode of action of lithium on electrical activity in the sympathetic ganglia of the bullfrog has been studied by recording extracellular and intracellular potential changes. Changes in nerve conduction and various types of synaptic transmission were studied when sodium ions in the external solution were totally replaced by equimolar concentrations of lithium ions and also when lithium ions were added to the external Ringer solution.2 Nerve conduction and nicotinic transmission in sympathetic ganglia were completely blocked in sodium-free sucrose solution, but were restored when the preparations were transferred to a sodium-free lithium solution.3 In the sodium-free lithium solution, the slow excitatory postsynaptic potential (e.p.s.p.) and muscarinic acetylcholine-depolarization were restored while the slow inhibitory postsynaptic potential (i.p.s.p.) and the muscarinic acetylcholine-hyperpolarization were not restored. Furthermore, the early after-discharges were accelerated and the inhibition of after-discharges was eliminated. These results support the hypothetical concept that the slow i.p.s.p. is generated by an activation of the electrogenic sodium pump.4 In the sodium-free lithium solution, restoration of nerve conduction and synaptic transmission were transient phenomena; both conduction and transmission were gradually blocked when preparations were soaked in the solution for long periods. The blockade appeared to be due to membrane depolarization.5 When lithium ions (20 mM) were added to the Ringer solution, nicotinic transmission was depressed. The slow e.p.s.p. was also depressed, but less so than the slow i.p.s.p. The early after-discharge was, however, accelerated; presumably due to the marked depression of the slow i.p.s.p. in this solution.6 Changes in synaptic transmission in Ringer solution containing lithium ions could be explained by membrane depolarization, a reduction of acetylcholine release and a depression of the electrogenic sodium pump.7 All results obtained in the present experiments could be explained by supposing that lithium ions are able to substitute for sodium ions in passive ionic membrane transport dependent on electrochemical energy but not in active ionic membrane transport dependent on metabolic energy.

Action Potentials↗

Lateral geniculate relay of slowly conducting retinal afferents to cat visual cortex.

1. Lateral geniculate neurones of the cat were studied in terms of the latency for activation by local electrical stimulation of the retina, the latency of electrical activation from the visual cortex and properties of receptive fields. Most of the units were relay cells (antidromic activation from visual cortex) but a small proportion were trans-synaptically activated from the cortex. The latter group included units with on-off, on-centre or off-centra receptive fields. 2. Direct activation of lateral geniculate neurones from local electrical stimulation of retinal ganglion cells or their axons in the retina was identified by the sharpness of timing of the elicited impulses. This procedure revealed the existence of slowly conducting axons relaying in the lateral geniculate nucleus. 3. The distribution of latencies for direct activation from the retina was bimodal with an extended tail of long values. It is similar to the distribution of antidromic latencies of retinal ganglion cells following stimulation of the optic tract. 4. There was a tendency for geniculate neurones with fast input from the retina to have fast axons to the visual cortex and correspondingly for medium-speed and slow input. 5. The previous classification of geniculate receptive fields into sustained and transient types was extended to include commonly encountered 'brisk' and uncommonly encountered 'sluggish' varieties of each. The extension was based on visual properties and latency for direct electrical activation from the retina. Units with receptive fields differing from the familiar on-centre or off-centre concentric pattern were encountered rarely; they included colour-coded fields, local-edge-detectors and one edge-inhibitory off-centre type.

Animals↗

Studies on the tachyphylaxis to nicotinic stimulant drugs in the perfused hypogastric ganglion of the guinea-pig.

1 The guinea-pig hypogastric ganglion, perfused through its vasculature with physiological saline solutions, will respond repeatedly to nicotinic stimulant drugs injected at 4 min intervals into the perfusion stream. Stimulation is indicated by contraction of the vas deferens. After a varying number of doses of nicotinic stimulants, complete tachyphylaxis usually develops, and normally this persists for at least 1 hour. During this time, however, electrical stimulation of the hypogastric nerve is still fully effective.2 Tachyphylaxis may be reversed for varying periods of time by all of the following procedures: (a) tetanic stimulation of the hypogastric nerve; (b) injection of large doses of histamine, methacholine, or potassium chloride; (c) perfusion with saline containing ouabain 0.1 mug/ml or 80-100 mM lithium chloride, or, to a lesser extent, with potassium-free saline.3 Tachyphylaxis is always re-established with further doses of nicotinic stimulants, except during perfusion with lithium solutions.4 Atropine hastens the onset of tachyphylaxis, but does not prevent its reversal by hypogastric nerve stimulation or by histamine or potassium. However, it does prevent the reversal by methacholine and by lithium.5 Tachyphylaxis occurs in decentralized ganglia, and can be reversed by histamine, methacholine, and by tetanic stimulation of the hypogastric ganglion. Hence tachyphylaxis and its reversal cannot be due to an effect on presynaptic fibres.6 Potassium chloride stimulates the ganglion both before and after tachyphylaxis has developed to nicotinic drugs, and hence this is unlikely to be due to a depolarization block.7 It is concluded that tachyphylaxis could be due to a prolonged ganglionic hyperpolarization.

Animals↗

Responses of rabbit retinal ganglion cells to electrical stimulation with an epiretinal electrode.

Rational selection of electrical stimulus parameters for an electronic retinal prosthesis requires knowledge of the electrophysiological responses of retinal neurons to electrical stimuli. In this study, we examined the effects of cathodal and anodal current pulses on the extracellularly recorded responses of OFF and ON rabbit retinal ganglion cells (RGCs) in an in vitro preparation. Current pulses (1 msec duration), delivered by a 125 microm electrode placed on the inner retinal surface within the receptive field of a RGC, produced both short-latency (< or =5 msec) and long-latency (8-60 msec) responses. The long-latency responses, but not the short-latency responses, were abolished upon application of the glutamate receptor antagonists CNQX and NBQX, thus indicating that the long-latency responses of RGCs are due to activation of presynaptic neurons in the retina. The latency of the long-latency response depended upon the polarity of the stimulus. For OFF RGCs, the average latency was 11 msec for a cathodal stimulus and 24 msec for an anodal stimulus. For ON RGCs, the average latency was 25 msec for a cathodal stimulus and 16 msec for an anodal stimulus. The threshold current also depended upon the polarity of the stimulus, at least for OFF RGCs. The average threshold current for evoking a long-latency response in OFF RGCs was 10 microA for a cathodal stimulus and 21 microA for an anodal stimulus. In ON RGCs, the average threshold current was 13 microA for a cathodal stimulus and 15 microA for an anodal stimulus.

Action Potentials↗

Hirschsprung's disease: a comparison of the nervous control of ganglionic and aganglionic smooth muscle in vitro.

Specimens from aganglionic (constricted) and ganglionic (dilated) gut were obtained from nine patients with Hirschsprung's disease. Transmural nerve stimulation of ganglionic smooth muscle in vitro evoked an initial relaxation followed by a contraction. This contraction was reduced but not abolished by atropine and it was further reduced by substance P antagonists. Guanethidine did not affect the electrically evoked responses. In aganglionic smooth muscle, an atropine-sensitive contraction but no initial relaxation was registered. Tetrodotoxin abolished all responses to electrical stimulation in both ganglionic and aganglionic specimens. Application of carbachol or substance P produced contraction and the adrenergic agonist isoprenaline or vasoactive intestinal peptide produced relaxation in ganglionic as well as aganglionic specimens. Two other gut neuropeptides, neuropeptide Y and galanin, were without effect. The results do not indicate a different receptor set up in ganglionic v aganglionic gut. The results are compatible with a lack of noncholinergic nonadrenergic inhibitory neurons in the aganglionic gut.

Child↗

Effect of amphetamine on the transmission of repetitive impulses through the isolated superior cervical ganglion of the rat.

1. The cervical sympathetic trunk of the isolated rat superior cervical ganglion was stimulated with short bursts of repetitive pulses. At room temperature with rates of stimulation of 4 Hz and above, the ganglionic action potentials were reduced in size.2. Amphetamine (2.7 x 10(-5)M), which caused some depression of transmission during stimulation at 0.1 Hz, caused a partial reversal of the depression of transmission occurring with rates of stimulation above 4 Hz.3. This action of amphetamine was mimicked by adrenaline (3 x 10(-5)M) and noradrenaline (9.6 x 10(-5)M) but not by isoprenaline (1.8 x 10(-5)M) and was unaffected by propranolol (1.4 x 10(-5)M) but was abolished by prior application of phenoxybenzamine (5.8 x 10(-6)M). Furthermore, this action of amphetamine was unaltered in ganglia taken from rats pretreated with reserpine (single dose of 6 mg/kg, 16 h before dissection).4. Amphetamine had no effect on the surface potentials of the ganglion or on changes in these potentials produced by concentrations of carbachol (5. x 10(-6)M to 5.5 x 10(-3)M).5. It is concluded that amphetamine has a direct action on alpha-adrenoceptors situated at presynaptic sites.

Action Potentials↗

Interactive atrial neural network: Determining the connections between ganglionated plexi.

BACKGROUND: The electrophysiologic functions of the intrinsic cardiac autonomic nervous system (ANS) are not well understood. OBJECTIVES: The purpose of this study was to investigate the functional interactions between ganglionated plexi within the intrinsic cardiac ANS. METHODS: The hearts of 21 dogs were exposed via right and/or left thoracotomy to expose the (1) anterior right ganglionated plexi near the caudal end of the sinoatrial node, (2) inferior right ganglionated plexi at the junction of inferior vena cava and atria, and (3) superior left ganglionated plexi near the junction of left superior pulmonary vein and left pulmonary artery. Ganglionated plexi were stimulated at 0.6 to 8.0 V (square waves, 20 Hz, 0.1-ms duration). Sinus rate, AH interval during atrial pacing, and ventricular rate during atrial fibrillation were compared before and after ganglionated plexi stimulation and after their ablation. RESULTS: Anterior right ganglionated plexi stimulation induced significant AH prolongation and slowing of ventricular rate and sinus rate. When inferior right ganglionated plexi was ablated, slowing of sinus rate by anterior right ganglionated plexi stimulation was unaltered, but inhibition of AV conduction was eliminated. Superior left ganglionated plexi stimulation induced similar effects on sinus and AV nodal function, and sinus rate slowing was markedly attenuated by anterior right ganglionated plexi ablation. Ablation of both anterior right ganglionated plexi and inferior right ganglionated plexi eliminated AV conduction inhibition but not sinus rate slowing by superior left ganglionated plexi stimulation. CONCLUSION: This study provides functional evidence for the interconnections between ganglionated plexi to modulate sinus and AV nodal function, supporting clinical evidence that interconnections within the intrinsic cardiac ANS are critical elements in identifying the targets for atrial fibrillation ablation.

Animals↗

[The neurite-outgrowth promoting effect from Clarke's nucleus of cat spinal cord with spared dorsal root preparation under electro-acupuncture stimulation on dorsal root ganglion of chicken embryo].

A modification of the double-coverslip hanging-drop culture technique originated from Maximow was introduced in the present report. The neurite - outgrowth promoting effect from Clarke's nucleus of cat spinal cord with partially lumbosacral dorsal rhizotomy as well as acupuncture stimulation of the points located within the peripheral innervating field of the spared dorsal root was examined with the modified culture technique. Findings demonstrated that an increased neurite-outgrowth promoting effect appeared in Clarke's nucleus of cat spinal cord with partial deafferentation, and that electro-acupuncture stimulation could enhance the neurite-outgrowth promoting effect further. It suggested that the increment of the neurite-outgrowth promoting effect might be related to the collateral sprouting of spared dorsal root and to the sprouting-promotion effect of acupuncture stimulation.

Animals↗

Localized and non-contact mechanical stimulation of dorsal root ganglion sensory neurons using scanning ion conductance microscopy.

Mechanosensitive ion channels convert external mechanical force into electrical and chemical signals in cells, but their physiological function in different tissues is not clearly understood. One reason for this is that there is as yet no satisfactory physiological method to stimulate these channels in living cells. Using the nanopipette-probe of the Scanning Ion Conductance Microscope (SICM), we have developed a new technique to apply local mechanical stimulus to living cells to an area of about 0.385 microm2, determined by the pipette diameter. Our method prevents any physical contact and damage to the cell membrane by use of a pressure jet applied via the nanopipette. The study used whole-cell patch-clamp recordings and measurements of intracellular Ca2+ concentration to validate the application of the mechanical stimulation protocols in human and rat dorsal root ganglia (DRG) sensory neurons. We were able, for the first time, to produce a non-contact, controlled mechanical stimulation on living neurites of human DRG neurons. Our methods will enable the identification and characterisation of compounds being developed for the treatment of clinical mechanical hypersensitivity states.

Adult↗

Afterdischarge on postganglionic sympathetic nerves following repetitive stimulation of the preganglionic nerve to the rat superior cervical ganglion in vitro.

An asynchronous firing or afterdischarge (AD) was recorded in vitro from the postganglionic internal carotid nerve of the rat superior cervical ganglion following repetitive stimulation of the preganglionic nerve when ganglion transmission was blocked by chlorisondamine, nicotine or hexamethonium, but was rarely observed in untreated ganglia. A stimulus frequency of at least 5 Hz was required to induce AD and as few as 100 pulses caused a significant response. The amplitude and duration of AD varied with the number of pulses. Low calcium solutions resulted in AD in the absence of ganglion blocking drugs, and high calcium solutions or low concentrations of atropine abolished the AD. Increasing magnesium concentration to 10 mM or the manganese concentration to 0.1 mM reduced or prevented AD following preganglionic nerve stimulation. The onset of AD was delayed in potassium-free solutions and at a lowered temperature. Dinitrophenol had a small depressant effect on AD but sodium azide reduced the amplitude significantly. Exposure of ganglia to bethanechol, 300 to 600 muM, resulted in asynchronous firing recorded from postganglionic nerves, and stimulation of the preganglionic nerve transiently depressed the drug-induced firing but enhanced the firing 30 to 60 seconds after the volley. Physostigmine did not alter the amplitude of bethanechol-induced firing after a volley. Prolonged high frequency (40 Hz) stimulation of the preganglionic nerve increased the AD following a 20 Hz test volley for up to 1 hour. It is concluded that increasing the release of acetylcholine or blockade of nicotinic receptors makes more acetylcholine available for interaction with muscarinic receptors, and that stimulation of the preganglionic nerve unmasks or sensitizes ganglionic muscarinic receptors. No clear evidence of a metabolic basis for the muscarinic response was obtained.

Animals↗

Information transmission rate changes of retinal ganglion cells during contrast adaptation.

During adaptation to high-contrast stimulation, retinal ganglion cell's responsiveness change is characterized by decreased firing rate and declined sensitivity. In order to examine the modification of information transmission properties of the ganglion cell during this adaptation process, neural activities were recorded extracellularly from the chicken retina using a multi-electrode recording system, and the information transmission rate of the retinal ganglion cells was estimated. The results show that the response entropy and noise entropy of the ganglion cells both decreased during the adaptation process, which resulted in a modest decline of information transmission rate of ganglion cells after several seconds' adaptation. However, due to the decrease of the neuron's firing rate during the adaptation, it is revealed that the information carried by each spike was increased as compared to pre-adaptation, suggesting that retinal ganglion cells' information processing strategies during contrast adaptation may reflect economical principle by promoting each spike more informative. These results also suggest that contrast adaptation and sensitivity rescaling of the visual neurons provide an efficient manner in information transmission and save the system's metabolic cost in the meantime.

Action Potentials↗

The influence of the frequency and pattern of sympathetic nerve activity on serotonin N-acetyltransferase in the rat pineal gland.

The activity of the pineal enzyme arylamine: N-acetyltransferase (NAT) was determined following direct stimulation of the preganglionic or post-ganglionic nerves of the superior cervical ganglia. 1. Stimulation of the preganglionic trunks at 10 c/sec during the day or night was sufficient to increase NAT activity approximately 50-fold, to levels comparable to those observed at night in the intact animal. The time course of this effect of nerve stimulation differed between day and night. 2. The responses of pineal NAT to certain frequencies of stimulation were similar for preganglionic and post-ganglionic stimulation. In both cases the responses to stimulation at 5 c/sec appeared to be maximal, 10 c/sec causing no further increase. However, at 10 c/sec, stimulation was more effective post-ganglionically than preganglionically. 3. Various patterns of preganglionic stimulation, having the same average frequency, differed in their ability to increase the activity of NAT. Some, though not all, of these differences between patterns were observed during post-ganglionic stimulation. 4. Unilateral stimulation of the preganglionic nerves produced an increase in NAT activity that was less than half the increase produced by bilateral stimulation, suggesting that the innervation from the two ganglia interact within the pineal gland. 5. These data indicate that changes in the firing rates of sympathetic nerves innervating the pineal gland, within the range of frequencies typically observed for sympathetic neurones, would be sufficient to account for the circadian rhythm in NAT activity observed in the intact rat. Changes in the over-all pattern of sympathetic activity, in addition to changes in the total number of stimuli, could play a significant role in the pineal response.

Acetyltransferases↗

Effect of hyperoxia on neurogenic plasma protein extravasation in the rat dura mater.

OBJECTIVE: We aimed to study the effect of normobaric hyperoxia on neurogenic inflammation of the rat dura mater. BACKGROUND: Inhalation of 100% oxygen is a first-line therapy for the treatment of acute cluster headache (CH). However, the mechanisms underlying the antinociceptive effect of oxygen are poorly understood. Sumatriptan, which is also effective in aborting CH attacks, is known to inhibit neurogenic inflammation of the dura mater. We hypothesized that hyperoxia reduces dural plasma protein extravasation in the model of electrically stimulating the rat trigeminal ganglion. METHODS: Unilateral stimulation of the trigeminal ganglion was performed in anesthetized male Sprague-Dawley rats. We assessed plasma protein extravasation (PPE) in the ipsilateral dura mater under normoxic (group 1) and hyperoxic conditions (group 2: pO(2) 200 mmHg; group 3: pO(2) 300 mmHg; group 4: pO(2) 400 mmHg). The study results were compared to the effect of sumatriptan (300 microg/kg) on dural PPE. RESULTS: Under normoxic conditions, the calculated extravasation ratio was 1.72 +/- 0.2. Hyperoxic treatment (groups 2, 3, 4) significantly attenuated dural PPE. At oxygen levels of 400 mmHg, the PPE ratio was 1.14 +/- 0.2 (P < .01). After IV application of sumatriptan (300 microg/kg), PPE was nearly abolished (PPE ratio: 1.06 +/-0.17). CONCLUSION: Our findings demonstrate that hyperoxia is able to inhibit dural PPE. Hyperoxia may play an anti-inflammatory role in neurogenic inflammation, but further studies are needed to clarify whether this effect is either caused by prejunctional mechanisms or by modulation of the vascular permeability at postcapillary venules.

Animals↗