Acetylcholine responses in L cells

L cells, a family of continuous cell lines of mouse fibroblastic origin, generate a prolonged active membrane hyperpolarization (the hyperpolarizing activation response) when stimulated mechanically or electrically. lontophoretically applied acetylcholine elicits a similar response; atropine blocks the acetylcholine but not the electrically or mechanically elicited responses. The hyperpolarizing activation response can also be elicited by electrical, mechanical, or acetylcholine stimulation of cells adjacent to the recorded cell. Propagation of the response from one cell to another is not dependent on direct electrical coupling between cells and is not blocked by application of a bath containing atropine or curare. These results show that L cells are capable of generating an active electrical response. that they are sensitive to at least one neurotransmitter (acetylcholine), and that humorally mediated interaction (probably noncholinergic) between L cells occurs.     

Depolarization and muscarinic excitation induced in a sympathetic ganglion by vasoactive intestinal polypeptide

The effects of vasoactive intestinal polypeptide (VIP) in the superior cervical ganglion of the cat were studied in vitro and in vivo with sucrose gap and multiunit recording, respectively. At a dose of 0.03 to 0.12 nanomole, VIP produced a dose-dependent, prolonged (3 to 15 minutes) depolarization of the ganglion and enhanced the ganglionic depolarization elicited by the muscarinic agonist acetyl-beta-methylcholine. At a dose of 1.8 to 10 nanomoles, the peptide enhanced and prolonged the postganglionic discharge elicited by acetyl-beta-methylcholine, enhanced muscarinic transmission in ganglia treated with an anticholinesterase agent, and enhanced the late muscarinic discharge elicited by acetylcholine. VIP did not affect the early nicotinic discharge elicited by acetylcholine or by electrical stimulation of the preganglionic nerve. It is concluded that VIP has a selective facilitatory action on muscarinic excitatory mechanisms in the superior cervical ganglion of the cat.     

Acetylcholine receptor synthesis in retina and transport to optic tectum in goldfish

Previous studies have suggested that the retinotectal system of the goldfish contains a nicotinic acetylcholine receptor (nAChR) that is sensitive to alpha-bungarotoxin. Extracellularly recorded field potentials elicited in response to visual stimulation can be blocked by alpha-bungarotoxin, and alpha-bungarotoxin can interfere with the maintenance of retinotectal synaptic connections. Whether the transmission between the retinal ganglion cells and the tectal cells is mediated by acetylcholine and whether nAChR's exist on the dendrites of tectal cells are questions that remain. The experiments described in this report were designed to determine the site of synthesis of the nAChR's associated with the goldfish retinotectal projection. Radioactive (35S-labeled) methionine was injected into either the eye or the tectal ventricle, and the incorporation of radioactivity into the nAChR was measured by immunoprecipitation. The use of this technique provides evidence that an nAChR associated with the goldfish retinotectal projection is synthesized in the retina and transported to the optic tectum, which suggests a presynaptic site of acetylcholine action on retinal terminals.     

Nicotine activation of alpha4* receptors: sufficient for reward, tolerance, and sensitization

The identity of nicotinic receptor subtypes sufficient to elicit both the acute and chronic effects of nicotine dependence is unknown. We engineered mutant mice with a4 nicotinic subunits containing a single point mutation, Leu9' --> Ala9' in the pore-forming M2 domain, rendering a4* receptors hypersensitive to nicotine. Selective activation of a4* nicotinic acetylcholine receptors with low doses of agonist recapitulates nicotine effects thought to be important in dependence, including reinforcement in response to acute nicotine administration, as well as tolerance and sensitization elicited by chronic nicotine administration. These data indicate that activation of a4* receptors is sufficient for nicotine-induced reward, tolerance, and sensitization.     

α6/α3β4乙酰胆碱受体在非洲爪蟾卵母细胞中的表达

α6/α3β4烟碱型乙酰胆碱受体（α6β4* nAChRs,*代表其他亚基）主要分布于大脑海马区、外周神经节和人源肾上腺嗜铬细胞等,与神经性疼痛和炎症反应、情绪等生理疾病密切相关。本研究拟对大鼠α6/α3β4 nAChR在非洲爪蟾（Xenopus laevis）卵母细胞膜上进行重组表达,并利用双电极电压钳电生理学技术检测该重组受体的功能。在不同浓度的激动剂乙酰胆碱的刺激下,比较了α6/α3和β4亚基的不同配比形成的受体通道开放而产生的电流大小,并用其拮抗剂α?芋螺毒素TxID验证了该受体的敏感性。结果表明,亚基不同配比的α6/α3β4 nAChR均可在非洲爪蟾卵母细胞膜上成功表达,并具有较好的配体门控敏感性。     

Somatostatin augments the M-current in hippocampal neurons

Immunocytochemical and electrophysiological evidence suggests that somatostatin may be a transmitter in the hippocampus. To characterize the ionic mechanisms underlying somatostatin effects, voltage-clamp and current-clamp studies on single CA1 pyramidal neurons in the hippocampal slice preparation were performed. Both somatostatin-28 and somatostatin-14 elicited a steady outward current and selectively augmented the noninactivating, voltage-dependent outward potassium current known as the M-current. Since the muscarinic cholinergic agonists carbachol and muscarine antagonized this current, these results suggest a reciprocal regulation of the M-current by somatostatin and acetylcholine.     

Destruction of mammalian motor nerve terminals by black widow spider venom

Black widow spider venom selectively poisons motor nerve endings. A progressive and irreversible failure of neuromuscular transmission occurs in the cat. Electron microscopy of the poisoned nerve-muscle junction shows a sequence of motor nerve ending damage that culminates in disruption of the prejunctional membrane and loss of all organelles, including synaptic vesicles. The postjunctional membrane was morphologically unaffected. After complete poisoning, the contractile response to exogenous acetylcholine was severely impaired, an indication that the prejunctional site is chiefly involved in the contractile response produced by exogenous acetylcholine and that the pre- and postjunctional effects of acetylcholine were separated.     

Receptive field mechanism in the vertebrate retina

In the catfish retina there are two types of ganglion cells: in one type (type A cell) a spot of light at the center of its receptive field gives rise to a sustained discharge whereas an annulus gives rise to a transient response, and in the other type (type B cell) the response pattern is reversed for a spot and an annulus. Current injected into the horizontal cell induces spike discharges of the ganglion cell very similar to that elicited by a spot of light or by an annulus. In both types of receptive fields, depolarization of the horizontal cell gives rise to a response of the ganglion cell similar to that elicited by a spot of light, whereas hyperpolarization of the cell gives rise to a response of the ganglion cell similar to that elicited by an annulus. Current through a single injecting electrode could drive two types of cells simultaneously. Interaction between a spot of light and an annulus can also be simulated by replacing one light stimulus by current of the proper polarization injected into the horizontal cells. Results suggest that interactions among three neuronal structures, the receptor, the horizontal cell, and the bipolar cell, produce the basic receptive field organization in the channel catfish.     

Sleep deprivation and brain acetylcholine

Rats deprived of D-state sleep (and, to some extent, of slow-wave sleep) for 96 hours show a significant fall in brain acetylcholine in the telencephalon; there were no significant changes in the diencephalon and brain stem. Restraint stress and activity wheel stress produced no significant change in acetylcholine levels in any of these regions; the telencephalic response to sleep deprivation, therefore, cannot be attributed to nonspecific stress. The effects of D-state deprivation and the psychoactive anticholinergic drugs on telencephalic acetylcholine levels are similar.     

Monoclonal antibody to acetylcholine receptor: cell line established from thymus of patient with Myasthenia gravis

A human B cell line producing a monoclonal antibody to an antigenic determinant of acetylcholine receptors was established by cloning B cells that had been transformed in vitro by Epstein-Barr virus. The B cells were obtained from the thymus of a patient with myasthenia gravis. The antibody produced by the cell line precipitated acetylcholine receptors from denervated and innervated rat muscle and from human muscle, but did not show detectable response to the acetylcholine receptors from the electric organs of Narke japonica. The monoclonal antibody showed identical binding patterns in innervated and denervated rat muscles. Passive transfer of the monoclonal antibody into rats induced moderate muscle weakness and electromyographic changes characteristic of myasthenia gravis.     

Early receptor potential: photoreversible charge displacement in rhodopsin

When the eye is illuminated by an intense flash, the visual pigment rhodopsin begins to pass rapidly through a series of intermediate states, eventually becoming bleached. If a second flash is delivered during the lifetimes of these intermediates the rhodopsin can be photoregenerated. A fast electrical response of the visual receptors, the early receptor potential, is elicited by the first flash. A similar response is elicited by the second flash, but the polarity of this response is reversed. Moreover, this response can be separated into three components, each arising from the action of light on a different intermediate. It is likely that all these fast responses, including the early receptor potential, arise from charge displacements in the visual-pigment molecule.     

CHARACTERISTICS OF HERBIVORY/WOUND-ELICITED ELECTRICAL SIGNAL TRANSDUCTION IN TOMATO

• Herbivory and mechanical wounding elicited electrical signals.• Petiole wounding elicited stronger electrical signals than did leaflet wounding.• Leaflet wounding elicited electrical signals and JA signaling within a compound leaf.• GLR3.3 and GLR3.5 mediated leaflet-to-leaflet electrical signal transduction.• JA synthesis and Helicoverpa armigera resistance were reduced in glr3.3/3.5 plants.Electrical signals commonly occur in plants in response to various environmental changes and have a dominant function in plant acclimation. The transduction of wound-elicited electrical signals in the model plant species Arabidopsis has been characterized but the characteristics of electrical signal transduction in response to herbivory or wounding in crop species remain unknown. Here, the features of electrical signals elicited by insect herbivory and wounding in tomato were investigated. Unlike those in Arabidopsis, wounding tomato leaves did not cause leaf-to-leaf electrical signal transduction. In contrast, electrical signals elicited in response to petiole wounding were stronger and more strongly transduced. Leaflet wounding also activated electrical signal transduction and jasmonic acid (JA) signaling within the whole compound leaf. It was also demonstrated that tomato glutamate receptor-like 3.3 (GLR3.3) and GLR3.5 mediated leaflet-to-leaflet electrical signal transduction. Herbivory-induced JA accumulation and Helicoverpa armigera resistance were reduced in glr3.3/3.5 plants. This work reveals the nature of electrical signal transduction in tomato and emphasizes the key roles of GLR3.3 and GLR3.5 in electrical signal transduction and JA signaling activation.     

Modulation of elicited behavior by a fixed-interval schedule of electric shock presentation

Responding elicited in the squirrel monkey by electric shocks presented every 60 seconds was gradually altered in temporal patterning, especially when the shock was also produced by responses under a 30-second fixed-interval schedule. The initially elicited pattern of maximal responding just after each shock was altered by the recurrent shock and by the added fixed-interval schedule to a pattern of maximal responding just before each shock. Most shocks were produced by responses and the response pattern was maintained for several months, but little responding occurred when shocks were omitted.     

Reduction of intestinal carcinogen absorption by carcinogen-specific secretory immunity

A secretory immune response to the carcinogen 2-acetylaminofluorene (AAF) was elicited in rabbits by directly immunizing the small intestine with an AAF-cholera toxin conjugate. High-titer, high-affinity secretory immunoglobulin A (IgA) antibody to AAF was secreted into the intestinal lumen in response to this immunogen. Immune secretions reduced the transepithelial absorption of a 125I-labeled derivative of AAF by more than half. This reduction of absorption by hapten-specific IgA suggests that oral vaccines against carcinogens and toxicants could be developed for humans.     

Cholinergic synaptic inhibition of inner hair cells in the neonatal mammalian cochlea

Efferent feedback onto sensory organs provides a means to modulate input to the central nervous system. In the developing mammalian cochlea, inner hair cells are transiently innervated by efferent fibers, even before sensory function begins. Here, we show that neonatal inner hair cells are inhibited by cholinergic synaptic input before the onset of hearing. The synaptic currents, as well as the inner hair cell's response to acetylcholine, are mediated by a nicotinic (alpha9-containing) receptor and result in the activation of small-conductance calcium-dependent potassium channels.     

Electrical phenomena associated with the activity of the membrane-bound acetylcholinesterase

Treatment of isolated electroplax with physiological solutions supplemented with either 1 molar sodium chloride, 2 molar urea, or 2 molar sucrose renders the cell insensitive to carbamylcholine, phenyltrimethylammonium, or decamethonium even at high concentrations. The treated cells have a residual resting potential of -20 +/- 10 millivolts (negative inside) and are depolarized by acetylcholine at concentrations larger than 10(-3) mole per liter. This response is not affected by d-tubocurarine but is blocked by physostigmine, diisopropylphosphorofluoridate, or strong buffers and thus depends on the catalytic activity of the membrane-bound acetylcholinesterase.     

Sex pheromones produced by male boll weevil: isolation, identification, and synthesis

The response of female boll weevils to males, Anthonomus grandis Boheman, in laboratory bioassays can be reproduced by exposure to a mixture of compounds I, II, and either III or IV, all isolated from male weevils and their fecal material. The same response was elicited by mixtures of tile synthesized coimpounds. Compound I is (+)-cis-2-isopropenyl-l-methylcyclobtutaneethanol; II, cis-3,3-dimethiyl->(1,beta)cyclohexaneethanol; III, cis-3,3-dimethlyl->(1,alpha)-cyclohexaneacetaldehyde; and IV, trans-3,3-dimethyl->(1,alpha)-cyclohexanecetaldehyde.     

Visual adaptation in monkey cones: recordings of late receptor potentials

The retinal cones of cynomolgus macaque monkeys show marked amounts of adaptation when the receptor potential is elicited by brief incremental stimuli presented against steady backgrounds of increasing intensity. The results can be accounted for by mechanisms of response compression, modified by the effects of photopigment bleaching, which together set the gain of the system at each background level, while also making the response nearly linear over a significant range of intensities above and below that of each adapting stimulus.     

Vesicular and synaptoplasmic synthesis of acetylcholine

The synthesis and distribution of acetylcholine has been studied in the isolated synaptosome. Binding or contamination of [(14)C]acetylcholine in the synaptic vesicle fraction represents 1.5 percent of the total amount found in the synaptoplasm (synaptosomal cytoplasm). However, when the [(14)C]acetylcholine is derived solely by synthesis from labeled choline, then the labeled acetylcholine in the synaptic vesicle is 15 percent of the amount of acetylcholine synthesized in the synaptoplasm. The results suggest that the [(14)C]acetylcholine found in the vesicle fraction of synaptosomes incubated with labeled choline is due to vesicular synthesis.     

Evoked potential correlates of generalization

Late components of evoked potentials recorded during the occurrence and nonoccurrence of generalization are different. During generalization the evoked response waveshapes resembled those elicited by the conditioned stimulus during correct performance. The differences are statistically significant.