UMLS:C0011570 - FACTA Search

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Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cat soleus motor nerve terminals, after high frequency conditioning, generate a post-tetanic repetition (PTR) which leads to a post-tetanic (PTP) of the muscle response. This property enables quantitative assessment of enhancement or depression of this nerve terminal excitability in vivo. The present study focuses on ionic mechanisms underlying the PTRs produced in this neuromuscular system either by high frequency stimulation or edrophonium. Ouabain was used as a specific probe for inhibition of Na(+)-K+ ATPase and its known consequences on Na+ and Ca2+ translocation. Ouabain pretreatment doubled the duration over which single stimuli, following either high frequency or edrophonium conditioning produced PTR. Ouabain in the doses used had no effect per se but as a function of dose augmented the frequency dependent responses. This pointed to Na+ loading of nerve terminals via high frequency stimulation plus ouabain inhibition of Na(+)-K+ ATPase. Ouabain potentiation of PTR responses evidently depends on exchange of intra-terminal sodium for external calcium. Thus, calcium entry blockers, Mn2+, and Co2+ suppressed or abolished the potentiations both before and after ouabain. Diphenylhydantoin, a Na+ and Ca2+ blocker, acted similarly. The effects of stimulation frequency, ouabain and the sequence of events leading to PTR in the soleus neuromuscular system appeared in general no different from those derived from the many in vitro microphysiologic studies of this phenomenon. Thus, EPPs were augmented and prolonged. It was concluded that intracellular Ca2+ is critical for regulating the stability of systems in which repetitive firing is both a normal and abnormal function.
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PMID:The interactions of ouabain with post-tetanic and facilitatory drug potentiations at cat soleus neuromuscular junctions in vivo. 216 59

1. The carotid body chemoreceptors are stimulated in situ by hypoxia. We have studied type I cells freshly dissociated from the carotid body of the rabbit. We have used microfluorimetric and patch clamp techniques to examine the responses to hypoxia, to anoxia, and to metabolic inhibition. 2. NADH autofluorescence measured at both 400 and 500 nm increased rapidly and reversibly in response to anoxia or to cyanide (CN-), reflecting a change in mitochondrial metabolism. 3. Indo-1 was used to measure changes in intracellular calcium, [Ca2+]i. Anoxia reversibly increased [Ca2+]i from approximately 50-100 to approximately 200-450 nM in all cells tested. The response showed a striking temperature sensitivity. Responses to hypoxic stimuli were barely detectable at 17-20 degrees C, and were dramatically increased on warming to 36 degrees C. In contrast, responses to K(+)-induced depolarization were only slightly increased in rate of onset and recovery by warming. 4. The rise in [Ca2+]i originated largely from an intracellular store which was slowly depleted by exposure to nominally Ca2(+)-free solutions. Responses were unaffected by blockade of Ca2+ channels with organic (D600, verapamil) or inorganic (Co2+) blockers, by blockade of Na+ channels with tetrodotoxin (TTX), or by increasing action potential duration with tetraethylammonium (TEA). Responses to anoxia were increased by the increased [Ca2+]i loading that follows prior exposure to Ca2(+)-free solutions. 5. Responses to anoxia, to blockade of electron transport by CN-, and to the mitochondrial uncoupler, carbonyl cyanide p-trifluoromethoxy-phenylhydrazone (FCCP), were equivalent in amplitude. The response to anoxia was occluded by concurrent application of FCCP, suggesting that the Ca2+ originates from the same pool in each case. 6. At 35-36 degrees C, responses to graded levels of PO2 were also graded. Thresholds varied between cells, but were typically 30-50 mmHg. Stimulus-responses curves were essentially hyperbolic, increasing dramatically as the PO2 approached 0 mmHg. 7. The sensitivity of cells to hypoxic solutions was increased by acidification of the superfusate over the pH range from 7.3 to 6.85. 8. Cell-attached patch clamp recordings showed depression of spontaneous action potentials associated with a rise in [Ca2+]i during exposure to anoxic solutions. Whole-cell recordings showed that anoxia increased a voltage-gated gK as described previously for CN-, while producing no change in resting conductance. 9. These data suggest that the rise in [Ca2+]i originates largely from Ca2+ efflux from a mitochondrial pool.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Responses of type I cells dissociated from the rabbit carotid body to hypoxia. 223 19

The action of the endogenous divalent cation zinc on Ca2+ and Ca2(+)-dependent currents was studied in rat hippocampal CA1 and CA3 neurons in vitro, by means of a single electrode voltage clamp technique. Bath application of zinc (0.5-1 microM) produced a small membrane depolarization associated with an increase in synaptic noise and cell excitability and a depression of the afterhyperpolarization following a train of action potentials. The effects on the afterhyperpolarization, could not be reversed on washout. In voltage-clamped neurons, zinc induced a steady inward current and reduced, at resting membrane potential, the peak amplitude of the outward current underlying the afterhyperpolarization, IAHP. In caesium loaded neurons (in the presence of tetrodotoxin and tetraethylammonium), zinc reduced the slow inactivating Ca2+ current activated from a holding potential of -40 mV. Similar results were observed with nickel and cobalt at comparable concentrations, with Zn2+ greater than Ni2+ greater than Co2+, in their order of potency. In contrast to nickel and cobalt the effects of zinc did not reverse on washout. These results suggest that low concentrations of zinc enhance cell excitability by reducing IAHP. In addition, zinc reduces the slow inactivating voltage-dependent Ca2+ current. The irreversible effect of this metal ion is compatible with a toxic, intracellular site of action.
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PMID:Submicromolar concentrations of zinc irreversibly reduce a calcium-dependent potassium current in rat hippocampal neurons in vitro. 223 3

The blocking effects of local anesthetics, mexiletine and disopyramide on the sodium currents (INa) of enzymatically isolated, single cells from rat ventricle were studied under voltage clamp conditions. A suction pipette technique was used for voltage clamp and internal perfusion. Potassium currents were blocked by replacing K+ with Cs+ in the internal and external solutions; calcium currents were blocked by replacing Ca2+ with Co2+ in the external solution to isolate INa. When the cells were stimulated infrequently (less than 1 Hz), both drugs produced dose-dependent depression of INa, which was correlated with one-to-one binding to sodium channel. A half-blocking concentration (KD) of 2.8 X 10(-5) M was observed for both agents. The shape of the current-voltage curve along the voltage axis remained unchanged in the presence of either drug. Both drugs shifted the inactivation curve of INa to more negative potentials. Mexiletine produced a marked use-dependent blockage of INa, whereas disopyramide did not produce significant use-dependent block under similar experimental conditions. Both drugs prolonged the recovery of INa from inactivation. The results suggested that both drugs interact with the inactivation mechanism of the sodium channels of rat myocardial cells.
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PMID:Blockage of the sodium current in isolated single cells from rat ventricle with mexiletine and disopyramide. 241 42

Staining deutocerebral nerves in locusts with cobalt chloride revealed a connective tissue strand innervated by the first side branch of the nervus scapalis medialis. The strand spans the joint between the basal segment of the antenna (scapus) and the head capsule (tentorium), parallel to the levator scapi muscle. It is shortest with the antenna completely elevated and becomes stretched during depression. The four to five neurons innervating the strand near its distal insertion are activated by mechanical stimuli such as direct elongation of the strand or depression of the antenna. As revealed by centripetal staining these neurons have their central arborizations in the posterior deutocerebrum, but their perikarya are located in the protocerebrum, close to the pars intercerebralis and the central body. These morphological and physiological characteristics identify the structure as a mechanoreceptive sense organ of the strand receptor class.
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PMID:Mechanoreceptive neurons in an insect brain. 241 31

Contribution of Ca2+-influx via the slow channel to generation of the transient inward current in guinea-pig ventricular muscles was studied using a single sucrose gap voltage clamp technique. The transient inward current (TI) was induced from superfusion of the preparations with the low-K+ (0 mM), high-Ca2+ (3.6 mM) solution. Application of 2 mM-CO2+ quickly and reversibly suppressed the TI amplitude to 25% of the control and delayed its peak timing to 153% during 10-20 min. Inhibition developed as quickly as Co2+ suppressed the slow inward current (Is), and its recovery took place without apparent time lag behind its effect on Is. The block of both TI and Is by Co2+ was antagonized by raising external Ca2+ to 7.2 mM. Removal of external Ca2+ caused a prompt suppression of both Is and TI. Application of 2 or 5 mM-procaine HCl produced a complete abolition of TI with a mild depression of Is. While 1 mM-caffeic caused a suppression of TI after a transient augmentation, 10 mM-caffeine completely eliminated it without abolishing Is. These results indicate that the Ca2+-influx through the slow channel acts not only to load the cell with those ions, but also to influence somehow the Ca2+-release from the stores under the Ca2+-overloaded conditions.
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PMID:Contribution of Ca2+-influx to generation of the transient inward current in guinea-pig ventricular muscles. 244 33

1. The effects of some divalent cations on the A-current (IA) in cultured rat dorsal root ganglion cells (DRGs) were studied using whole-cell patch recording. 2. IA was not affected by omission of calcium from the external medium; however it was significantly depressed by manganese (10 mM) applied by pressure ejection. This depressant effect of manganese resulted from a depolarizing shift of the activation curve by 17 mV, associated with only a slight reduction of the maximum conductance. At 10 mM manganese also caused a depolarizing shift of the steady-state inactivation curve by 34 mV. Divalent cations other than manganese also gave positive shifts of the steady-state activation and inactivation curves for IA but were of different potency; the sequence was: Cd2+ greater than Mn2+ = Co2+ greater than Mg2+. 3. A dose-response curve for the depolarizing shift of the activation and inactivation curves of IA, as a function of manganese concentration, could be fitted by a single binding site model with an apparent dissociation constant of approximately 17 mM. The depolarizing shift of the inactivation curve was on average twice as large as that of the activation curve. 4. In contrast to its effect on IA, manganese (10 mM) did not cause any appreciable change in the voltage dependence of the activation curve for the delayed rectifier K+ current. 5. A low concentration of manganese (1 mM) increased the amplitude of IA recorded at pre-pulse potentials ranging from -50 to -70 mV. This augmentation of IA resulted from a positive shift of the inactivation curve by 6 mV without an appreciable shift of the activation curve; as a result a population of A-channels is released from inactivation over pre-pulse potentials from -50 to -70 mV. 6. These results show that divalent cations can evoke a depolarizing shift of both the activation and inactivation gates controlling IA; this causes either depression or augmentation of IA, depending on the species and concentration of the divalent cation, and also on the pre- pulse potential used to de-inactivate IA. This modulatory effect of divalent cations on the gating of IA appears to reflect binding to a specific, saturable site, either the A-channel protein itself, or phospholipids electrically close to the gating apparatus.
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PMID:A modulatory action of divalent cations on transient outward current in cultured rat sensory neurones. 245 91

The voltage- and time-dependent slow channels in the myocardial cell membrane are the major pathway by which Ca2+ ions enter the cell during excitation for initiation and regulation of the force of contraction of cardiac muscle. These slow channels appear to behave kinetically, on a population basis, as if their gates open, close, and recover more slowly than those of the fast Na+ channels. In addition, the slow channel gates operate over a less negative (more depolarized) voltage range. Tetrodotoxin does not block the slow channels, whereas the calcium antagonistic drugs, Mn2+, Co2+, and La3+ ions do. The slow channels have some special properties, including functional dependence on metabolic energy, selective blockade by acidosis, and regulation by the intracellular cyclic nucleotide levels. Because of these special properties of the slow channels, Ca2+ influx into the myocardial cell can be controlled by extrinsic factors (such as autonomic nerve stimulation or circulating hormones) and by intrinsic factors (such as cellular pH or ATP level). During transient regional ischemia, the selective blockade of the slow channels, which results in depression of the contraction and work of the afflicted cells, might protect the cells against irreversible damage by helping to conserve their ATP content. Reperfusion arrhythmias may be caused by the breakdown of this protective mechanism, in that, upon reperfusion, the Ca2+ slow channels may recover before the cells are capable of handling the greater Ca2+ influx (Fig. 20). As depicted in this figure, the Ca2+ slow channels may recover their function before the ATP level is sufficiently recovered to allow bail-out of the intracellular Ca2+. In addition, the generation of free radicals upon reperfusion may injure the Ca-ATPase and other enzymes involved in Ca2+ metabolism. The net effect of this would be to cause Ca2+ overload of the cells and SR, with subsequent delayed after-depolarizations (DADs) leading to triggered automaticity and arrhythmias. Following blockade of the fast Na+ channels in myocardial cells with TTX or by voltage-inactivating them in 25 mM (K)0, catecholamines, angiotensin-II, histamine, and methylxanthines rapidly allow the production of slowly-rising Ca2+-dependent action potentials by increasing the number of Ca2+ slow channels available for voltage activation and/or their mean open time. Concomitantly, these compounds rapidly elevate intracellular cyclic AMP levels, suggesting that cyclic AMP is somehow related to the functioning of the slow channels. Exogenous cyclic AMP produces the same effect, but much more slowly.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Regulation of calcium slow channels of cardiac muscle by cyclic nucleotides and phosphorylation. 245 7

1. Propagated Ca-spikes were recorded from isolated cervical sympathetic nerve trunks of the rat when bathed in a solution containing 5 mM Ca2+, 0.5 or 1 microM tetrodotoxin (to block Na currents) and 1 mM 4-aminopyridine (to reduce K currents). 2. Spikes persisted when external Ca2+ was replaced with Sr2+ or Ba2+, but were blocked by the addition of the following inorganic Ca-channel blockers (in descending order of potency): Cd2+ greater than La3+ greater than Ni2+ greater than Co2+ greater than Mn2+ greater than Mg2+. 3. Ca-spike amplitude was reduced by up to 90% by (-)-noradrenaline (IC50 1.5 microM). The following sympathomimetic amines imitated this effect (in descending order of potency): clonidine greater than or equal to (-)-adrenaline greater than or equal to [(-)-noradrenaline] greater than or equal to dopamine greater than (-)-phenylephrine greater than or equal to (+/-)-amidephrine. 4. Ca-spike inhibition by (-)-noradrenaline was antagonized by phentolamine (pA2 6.5). Yohimbine was about 10 times weaker than phentolamine; (+/-)-propranolol (1 microM) and prazosin (10 microM) had no clear effect. 5. (-)-Noradrenaline reduced the amplitude of the compound action potential recorded from the superior cervical sympathetic ganglion following supramaximal preganglionic trunk stimulation when recorded in normal Krebs solution and hyperpolarized the ganglion with respect to the post-ganglionic trunk. Depression of the transmitted ganglionic action potential was antagonized by phentolamine (5 microM) but not by yohimbine (1 microM); in contrast 1 microM yohimbine completely prevented the ganglionic hyperpolarization. (-)-Noradrenaline did not hyperpolarize the preganglionic cervical sympathetic nerve trunk under these recording conditions. 6. It is suggested that inhibition of transmitter release from sympathetic preganglionic fibres produced by noradrenaline results from a depression of the voltage-gated Ca current in the fibres and/or their terminals, and that this action is mediated by an alpha-adrenoceptor which does not fully conform to either alpha 1 or alpha 2 subtypes.
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PMID:Inhibition of Ca-spikes in rat preganglionic cervical sympathetic nerves by sympathomimetic amines. 253 83

The effects on isometric tension of three divalent ions that block calcium channels, magnesium, cobalt, and cadmium, were tested in small bundles of rat soleus fibers. Cobalt, at a concentration of 2 or 6 mM, reversibly depressed twitch and tetanic tension and the depression was much greater in solutions containing no added calcium ions. Magnesium caused much less depression of tension than cobalt. The depression of tension was not accompanied by membrane depolarization or a reduction in the amplitude of action potentials. A reduction caused by 6 mM cobalt in the amplitude of 40 or 80 mM potassium contractures was not accompanied by a comparable reduction in tension during 200 mM potassium contractures, and could be explained by a shift in the potassium contracture tension-voltage curve to more positive potentials (by +7 mV on average). Similar effects were not seen with 2 or 6 mM magnesium. At a concentration of 20 mM, both cobalt and magnesium depressed twitch and tetanic tension, cobalt having greater effect than magnesium. Both ions shifted the potassium contracture tension-voltage curve to the right by +5 to +10 mV, caused a small depression of maximum tension, and slowed the time course of potassium contractures. Cadmium (3 mM) depressed twitch, tetanic, and potassium contracture tension by more than 6 mM cobalt, but experiments were complicated by the gradual appearance of large contractures that became even larger, and sometimes oscillatory, when the solution containing cadmium was washed out. It was concluded that divalent cations affect both activation and inactivation of tension in a manner that cannot be completely explained by a change in surface charge.
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PMID:Effects of cobalt, magnesium, and cadmium on contraction of rat soleus muscle. 275 79

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