Preganglionic stimulation increases calcium uptake by sympathetic ganglia

Isolated superior cervical ganglia of rats accumulate more calcium during preganglionic stimulation than do unstimulated controls; uptake of calcium-45 is approximately doubled by stimulation of 12 impulses per second. The extra uptake is markedly reduced by a high concentration of magnesium, but not by mecamylamine hydrochloride or tetraethylammonium chloride, although all three agents eliminate the postsynaptic action potential. Uptake of calcium-45 is also greatly increased by a high external concentration of potassium.     

Electrical stimulation of the amygdala as a conditioned stimulus in a bait-shyness paradigm

Animals receiving low-intensity electrical stimulation of the basolateral nucleus of the amygdala while drinking plain tap water were injected with toxic doses of lithium chloride to examine whether brain stimulation can serve as a conditioned stimulus in a bait-shyness paradigm. Subjects receiving this pairing greatly reduced their water intake in a retention test, in a similar manner to a group in which saccharin was paired with poisoning. Pairing lithium chloride with stimulation of the amygdala had no effect on subsequent water intake in the absence of brain stimulation. This effect appears to be locus specific, as caudate stimulation could not serve as a conditioned stimulus.     

Altered regulation of airway epithelial cell chloride channels in cystic fibrosis

In many epithelial cells the chloride conductance of the apical membrane increases during the stimulation of electrolyte secretion. Single-channel recordings from human airway epithelial cells showed that beta-adrenergic stimulation evoked apical membrane chloride channel activity, but this response was absent in cells from patients with cystic fibrosis (CF). However, when membrane patches were excised from CF cells into media containing sufficient free calcium (approximately 180 nanomolar), chloride channels were activated. The chloride channels of CF cells were similar to those of normal cells as judged by their current-voltage relations, ion selectivity, and kinetic behavior. These findings demonstrate the presence of chloride channels in the apical membranes of CF airway cells. Their regulation by calcium appears to be intact, but cyclic adenosine monophosphate (cAMP)-dependent control of their activity is defective.     

Visual receptor potential: modification by injected current in the limulus lateral eye

The latent period of the light-evoked receptor potential was increased by hyperpolarizing currents injected directly into doubly impaled retinular cells. Indirect hyperpolarization of these cells by injection of hyperpolarizing current into the eccentric cell or other intraommatidial retinular cells either shortened or did not change the latent period. The modification of the latent period may depend upon the direction of current flow across some regions of the membrane system constituting the rhabdomere. The reduction in magnitude of the receptor potential obtained with strong hyperpolarizing currents may also depend upon the direction of current flow. The results support the conclusion that the receptor potential originates in retinular cells within the membrane system of the rhabdomere.     

Odor-induced membrane currents in vertebrate-olfactory receptor neurons

In olfactory receptor neurons, odor molecules cause a depolarization that leads to action potential generation. Underlying the depolarization is an ionic current that is the earliest electrical event in the transduction process. In two preparations, olfactory receptor neurons were voltage-clamped and stimulated with odors and this generator current was measured. In addition, a method was developed to estimate the time course and absolute concentration of odorants delivered to the receptor sites. With this method, olfactory neurons were found to have relatively high stimulus thresholds, steep dose-response relations, long latencies, and an apparent requirement for cooperativity at one or more steps in the pathway from odorant binding to activation of the generator current.     

Muscarinic modulation of cardiac rate at low acetylcholine concentrations

Slowing of cardiac pacemaking induced by cholinergic input is thought to arise from the opening of potassium channels caused by muscarinic receptor stimulation. In mammalian sinoatrial node cells, however, muscarinic stimulation also inhibits the hyperpolarization-activated current (If), which is involved in the generation of pacemaker activity and its acceleration by catecholamines. Acetylcholine at nanomolar concentrations inhibits If and slows spontaneous rate, whereas 20 times higher concentrations are required to activate the acetylcholine-dependent potassium current (IK,ACh). Thus, modulation of If, rather than IK,ACh, is the mechanism underlying the muscarinic control of cardiac pacing at low (nanomolar) acetylcholine concentrations.     

Diphasic postsynaptic potential: a chemical synapse capable of mediating conjoint excitation and inhibition

Two identified interneurons in each buccal ganglion of Aplysia can mediate conjoined excitation and inhibition to a single follower cell. A single presynaptic action potential in one of these interneurons produces a diphasic, depolarizing-hyperpolarizing synaptic potential apparently as a result of a single transmitter acting on two types of postsynaptic receptors in the follower cell. These receptors produce synaptic potentials with differing reversal potentials, ionic conductances, time courses, rates of decrement with repetition, pharmacological properties, and functional consequences. The excitatory receptor controls a sodium conductance, the inhibitory receptor controls a chloride conductance. Both components of the synaptic potentials can be produced by iontophoretic application of acetylcholine on the cell body of the follower cell, and each component is differentially sensitive to different cholinergic blocking agents.     

Stomatal opening: role of potassium uptake by guard cells

Stomata in isolated epidermal strips open in response to light plus air free of carbon dioxide when the strips are floated on potassium chloride solutions of low concentrations. This opening depends on the stimulation of active accumulation of potassium in quantities sufficient to account for the observed changes in solute potential of the guard cells.     

Tetraethylammonium and tetrodotoxin: effects on cochlear potentials

Tetraethylammonium chloride, which is believed to decrease potassium conductance, and tetrodotoxin, which apparently decreases sodium conductance in nerve fibers, were introduced iontophoretically into the organ of Corti or the scala media of guinea pig cochlea. The former depressed the direct-current endocochlear potential and also the alternating-current cochlear microphonics (the receptor potential of the ear), but tetrodotoxin was ineffective except on the nerve impulses.     

Membrane origin of the fast photovoltage of squid retina

When a bright light flash is absorbed by a small region in the outer segments of squid photoreceptors fixed in glutaraldehyde, a brief pulse of membrane current flows locally. The passive spreading of this current along the outer segments produces the photochemical component of the "early receptor potential." The source of the current lies electrically in parallel with the cell membranes and perhaps is located within them. Fixation with glutaraldehyde apparently does not reduce the resistance of the cell membrane to less than 5 percent of its value in live cells.     

A voltage-dependent chloride current linked to the cell cycle in ascidian embryos

A voltage-dependent chloride current has been found in early ascidian embryos that is a minor conductance in the oocyte and in interphase blastomeres but that increases transiently in amplitude by more than tenfold during each cell division. Repeated cycles in the density of this chloride current could be recorded for up to 6 hours (four cycles) in cleavage-arrested embryos, whether they were activated by sperm or calcium ionophore. These data suggest that there is a direct link between the cell cycle clock and the properties of this channel, a link that results in pronounced cyclical changes in the electrical properties of early blastomeres.     

Direct demonstration of macula densa-mediated renin secretion

An in vitro method has been used to examine whether secretion of renin from the juxtaglomerular apparatus is affected by changes in the sodium chloride concentration of the tubular fluid at the macula densa. Single juxtaglomerular apparatuses were microdissected from rabbits and the tubule segment containing the macula densa was perfused, while simultaneously the entire juxtaglomerular apparatus was superfused, and the fluid was collected for renin measurement. In this preparation, in which influences from renal nerves and local hemodynamic effects are eliminated, a decrease in the tubular sodium chloride concentration at the macula densa results in a prompt stimulation of the renin release rate.     

Tetrodotoxin: effects on brain metabolism in vitro

A 3-micromolar concentration of tetrodotoxin completely inhibits the stimulation of respiration of rat brain cortex that takes place upon application of electrical impulses. It also inhibits increase in the rate of the respiration that occurs when calcium ions are omitted from the incubation medium. No effect of tetrodotoxin on brain respiration takes place when stimulation is brought about by the addition of 100 millimolar potassium chloride. Tetrodotoxin prevents the fall in the rate of oxidation of cerebral acetate that occurs during electrical stimulation but does not affect the increased rate of the oxidation that occurs in the presence of an increased concentration of potassium chloride. The data indicate that oxidation of cerebral acetate is diminished by influx of sodium ions, which is prevented by tetrodotoxin, and is increased by influx of potassium ions, which is unaffected by tetrodotoxin.     

Autocrine stimulation of intracellular PDGF receptors in v-sis-transformed cells

Autocrine activation of platelet-derived growth factor (PDGF) receptors is the mechanism of transformation by the v-sis oncogene. Since the addition of PDGF does not transform normal cells, autocrine mechanisms may involve unique pathways of receptor activation. In this study autocrine stimulation of the PDGF receptor was observed in v-sis-transformed normal rat kidney (NRK) cells. In contrast to receptor activation in normal cells, autocrine activation of PDGF receptors in v-sis-transformed cells occurred in intracellular compartments, disrupting receptor processing and diverting receptors and their precursors to a chloroquine-sensitive degradation pathway. These findings show that intracellular activation of receptors by autocrine mechanisms may play a role in cell transformation.     

Extracellular potassium ions mediate specific neuronal interaction

The giant interneurons from the nerve system of the cockroach Periplaneta americana exhibit a peculiar reciprocal synaptic interaction. The synaptic potentials are not blocked by addition of 5 millimolar cobalt chloride and have an extrapolated reversal potential close to 0 millivolt. Hyperpolarizing current injected into one cell does not spread to the other. Intracellular injection of tetraethylammonium ions into one giant interneuron increases the duration of the action potential of the injected cell to 30 milliseconds and reduces the rise time and amplitude of the postsynaptic response recorded in the other giant interneuron. These results indicate that the interaction between the interneurons is not mediated by conventional chemical or electrotonic synapses.. All evidence points to generation of the potentials by localized increases in extracellular potassium concentrations as a consequence of firing of one neuron.     

电针内关穴预处理对心肌缺血再灌注损伤大鼠线粒体膜电位、腺苷A1受体的影响

目的 观察电针内关预处理对心肌缺血再灌注损伤（myocardial ischemicreperfusion injury, MIRI）大鼠心肌线粒体膜电位、腺苷A1受体的影响,探讨电针预处理防治MIRI的可能作用机制。方法 40只SD雄性大鼠随机分为假手术、缺血再灌注组（模型组）、电针内关穴组、电针环跳穴组,每组10只。采用冠脉结扎法造模,电针内关组和电针环跳穴组在造模前,给予电针刺激 20 min/d,共7d。采用荧光技术测定心肌细胞线粒体膜电位变化,免疫组化法测腺苷A1受体的表达。结果 模型组线粒体膜电位及腺苷A1受体较假手术组明显下降（P<0.01）;电针内关穴组线粒体膜电位较模型组、电针环跳穴组及假手术组明显升高（P<0.05）;电针内关组腺苷A1受体较模型组、电针环跳穴组和假手术组明显升高（P<0.01）;模型组与电针环跳组间无明显差异（P>0.05）。结论 电针内关穴预处理可以诱导腺苷A1受体的表达,升高线粒体膜电位,对心肌细胞产生保护作用。     

Ethanol inhibits NMDA-activated ion current in hippocampal neurons

The ion current induced by the glutamate receptor agonist N-methyl-D-aspartate (NMDA) in voltage-clamped hippocampal neurons was inhibited by ethanol (EtOH). Inhibition increased in a concentration-dependent manner over the range 5 to 50 mM, a range that also produces intoxication. The amplitude of the NMDA-activated current was reduced 61 percent by 50 mM EtOH; in contrast, this concentration of EtOH reduced the amplitude of current activated by the glutamate receptor agonists kainate and quisqualate by only 18 and 15 percent, respectively. The potency for inhibition of the NMDA-activated current by several alcohols is linearly related to their intoxicating potency, suggesting that alcohol-induced inhibition of responses to NMDA receptor activation may contribute to the neural and cognitive impairments associated with intoxication.     

Lead effects on corn mitochondrial respiration

Oxidation of exogenous nicotinamide-adenine dinucleotide and succinate by corn mitochondria was measured as a function of lead chloride concentration. Lead chloride (50 to 62 micromoles per liter) stimulated oxidation of exogenous reduced nicotinamide-adenine dinucleotide by 174 to 640 percent depending on the reaction mediums, whereas lead chloride (12.5 micromoles per liter) inhibited succinate oxidation by more than 80 percent. When inorganic phosphate was included in reaction mediums the subsequent addition of lead was without effect due to the low solubility of lead phosphate. If addition of lead was followed by addition of phosphate the inhibition of succinate oxidation by lead was released, but there was no reduction in the stimulation of oxidation of reduced nicotinamide-adenine dinucleotide by lead. The effects of lead on plant growth might be accentuated under conditions of phosphate deficiency.     

TMEM16A, a membrane protein associated with calcium-dependent chloride channel activity

Calcium-dependent chloride channels are required for normal electrolyte and fluid secretion, olfactory perception, and neuronal and smooth muscle excitability. The molecular identity of these membrane proteins is still unclear. Treatment of bronchial epithelial cells with interleukin-4 (IL-4) causes increased calcium-dependent chloride channel activity, presumably by regulating expression of the corresponding genes. We performed a global gene expression analysis to identify membrane proteins that are regulated by IL-4. Transfection of epithelial cells with specific small interfering RNA against each of these proteins shows that TMEM16A, a member of a family of putative plasma membrane proteins with unknown function, is associated with calcium-dependent chloride current, as measured with halide-sensitive fluorescent proteins, short-circuit current, and patch-clamp techniques. Our results indicate that TMEM16A is an intrinsic constituent of the calcium-dependent chloride channel. Identification of a previously unknown family of membrane proteins associated with chloride channel function will improve our understanding of chloride transport physiopathology and allow for the development of pharmacological tools useful for basic research and drug development.     

Amantadine: neuromuscular blockade by suppression of ionic conductance of the acetylcholine receptor

Amantadine hydrochloride decreases the sensitivity of denervated mammalian muscle to iontophoretically applied acetylcholine. The drug depresses the amplitude of the end-plate current and reverses the slope of the relation between half-decay time and membrane potential suggesting that it alters the ionic conductance that is mediated by the acetylcholine receptor. Binding studies confirm that amantadine acts on the ion conductance modulator rather than the acetylcholine receptor.