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

The role and regulation of (Na, K)-ATPase in cardiac sarcolemma are relatively well recognized today. Less abundant information is available about the time sequence of ischaemia-induced changes in activity and properties of the enzyme. In our experiments global ischaemia to the rat heart induces a time-dependent decrease in the activity and maximum velocity (Vm) value of sarcolemmal (Na, K)-ATPase. The depression of enzyme activity is fast and is expressed as early as 15 min after the onset of ischaemia. After 30 min of ischaemia the Vm decrease slows, probably due to an 'adaptational' decrease of the Km value of the (Na, K)-ATPase. This phenomenon may be interpreted as a mechanism by which the enzyme attempts to keep functioning in a situation when the supply by ATP is deficient. The depression in (Na, K)-ATPase activity is an early indicator of sarcolemmal damage. It outruns the changes in permeability of the cardiac sarcolemma to calcium and predicts ultrastructural damage to myocytes induced by ischaemia.
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PMID:Features of the (Na, K)-ATPase of cardiac sarcolemma with particular reference to myocardial ischaemia. 166 53

1. The whole-cell patch-clamp technique was used to record membrane currents from neurones which were acutely dissociated from the intra-atrial parasympathetic ganglia of Rana pipiens. The effects of muscarine and adrenaline were observed at a holding potential of -30 mV. Extracellular potassium concentration ([K+]o) was 2, 6 or 20 mM. 2. Muscarine (10 microM) produced inward current in thirteen cells, outward current in eighteen cells and seven cells were unaffected. Inward currents were observed in six out of ten neurones in which the intracellular solution contained adenosine triphosphate (ATP; 100 microM) and outward currents were seen in eleven out of fourteen neurones which contained adenosine 3',5'-cyclic monophosphate (cyclic AMP; 100 microM). 3. In five out of nine cells tested, the inward current produced by muscarine was attributable to a 30% depression of a voltage-dependent current which resembled the M-current (IM). Muscarine-induced inward current in the other four cells involved a steady-state conductance increase that reached a null potential at -10 mV. Modest IM suppression also contributed to the response in three of these four cells. 4. Adrenaline (10 or 100 microM) produced inward currents in twelve cells, outward current in ten cells and three cells were unaffected. Outward currents were only seen in cells which contained ATP or cyclic AMP (ten out of sixteen cells) whereas inward currents were seen in eight out of nine cells which did not contain adenosine nucleotides. These inward currents were always attributable to IM suppression. 5. The outward currents induced by muscarine and adrenaline resulted from an increase in a potassium conductance (GK) that exhibited inward rectification.
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PMID:The effects of muscarine and adrenaline on patch-clamped frog cardiac parasympathetic neurones. 166 40

The present study was undertaken to elucidate the possible actions of yohimbine on cardiac function and metabolism in the hypoxic and subsequently reoxygenated myocardium. For this purpose, rabbit hearts were perfused for 20 min under hypoxic conditions, followed by 45 min reoxygenated perfusion, and their functional and metabolic alterations with and without yohimbine treatment were examined. Hypoxia induced cessation of cardiac contractile force, rise in resting tension and depletion of tissue high-energy phosphates, which were poorly recovered by subsequent reoxygenation. Hypoxia also induced release of creatine kinase and ATP metabolites from perfused hearts and increases in tissue calcium and sodium contents, which were further enhanced upon subsequent reoxygenation. When hypoxic hearts were treated with 3 to 30 microM yohimbine, several beneficial effects were observed in a concentration-dependent manner. This included enhancement of posthypoxic recovery of contractile function and suppression of the hypoxia- and reoxygenation-induced rise in resting tension. Hypoxia/reoxygenation-induced release of ATP metabolites was inhibited and restoration of myocardial high-energy phosphates enhanced. Inhibition of reoxygenation-induced rise in tissue calcium and sodium and creatine kinase release were also noted. The findings suggest that suppression of transmembrane flux of ions, substrates and enzymes during hypoxia/reoxygenation plays a role in the posthypoxic functional and metabolic recovery. Yohimbine (3-30 microM) significantly depressed the maximal stimulus frequency the left atria could follow. These results suggest a close relationship between depression in the maximal driving frequency of atria and enhancement of the posthypoxic contractile and metabolic recovery of perfused hearts.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Beneficial effects of yohimbine on posthypoxic recovery of cardiac function and myocardial metabolism in isolated perfused rabbit hearts. 167 45

1. The rate of oxygen consumption has been monitored continuously in M. edulis during acute exposure to high sublethal concentrations of formaldehyde, phenol and benzene and subsequent recovery periods of 96 hr. 2. The results are discussed in relation to changes in the electrochemical potential difference of sodium, the content of ATP and the tissue concentration of strombine. 3. After exposure to benzene and phenol, an increase in the rate of oxygen consumption that could not be explained by oxygen debt from the exposure period was observed. 4. Depression of the rate of oxygen consumption after exposure to formaldehyde may be explained by a reduced ability to extract oxygen from the water. 5. The pattern of oxygen consumption and behavioural responses, as well as the combined changes in the biochemical markers, were distinctly different in the three cases.
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PMID:Measurements of oxygen consumption in Mytilus edulis during exposure to, and recovery from, high sublethal concentrations of formaldehyde, benzene and phenol. 167 79

1. Endogenous adenosine, which is produced by enzymatic degradation of ATP released from synaptic vesicles, has been shown to be a potent inhibitor of acetylcholine release from motor nerve terminals. It has been proposed that this auto-inhibition mechanism might contribute significantly to tetanic stimulation-induced depression. 2. Levels of facilitation and depression during a 20 Hz stimulus train differ greatly in different terminals, but are strongly and non-linearly correlated with the terminal's release characteristics (the amount of transmitter released per unit terminal length, or 'release efficacy'). There is a weaker, approximately linear, correlation between depression and release efficacy at 2 Hz stimulation. 3. The effects of both endogenous and exogenously applied adenosine are also highly variable for different nerve terminals. We have shown that much of this variability can be attributed to the release efficacy of each terminal in the case of endogenous effects, and to the size of the nerve terminal in the case of exogenously applied adenosine receptor agonists. 4. When nerve terminals are pooled according to their individual release characteristics, endogenous adenosine can be shown to contribute significantly to stimulation-induced depression of release primarily in terminals that release enough transmitter to generate significant levels of adenosine, but do not release so much transmitter that depletion of releasable quanta is severe.
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PMID:Endogenous adenosine modulates stimulation-induced depression at the frog neuromuscular junction. 168 26

Previous studies in our laboratory have shown that cromakalim activates a tetraethylammonium-sensitive K+ current in cultured embryonic rat hippocampal neurons. This phenomenon was further characterized using whole-cell voltage-clamp and single-channel recording techniques. Glyburide (1-25 microM), an antagonist of ATP-sensitive K+ channels, produced a concentration-dependent depression of the cromakalim-activated current. In contrast, charybdotoxin (100 nM), an antagonist of some Ca(2+)-dependent and other K+ channels, not only failed to block the effect of cromakalim but actually produced a moderate enhancement of the cromakalim-activated K+ current. Neither glyburide nor charybdotoxin affected resting or voltage-activated K+ currents in the absence of cromakalim. Exposure of the cells to energy-depleting conditions (0.24 micrograms/ml oligomycin and 10 mM 2-deoxy-D-glucose) also activated an outward current. Single-channel recordings in the cell-attached configuration showed that cromakalim (100 microM) stimulated the opening of flickery single channels having a unitary conductance of approximately 26 pS and a prolonged burst duration (mean open time, approximately 131 msec); similar channel openings were observed in patches from cells exposed to energy-depleting conditions. In patches containing a single K+ channel, the open probability in the presence of cromakalim was approximately 0.6 and in the presence of energy-depleting conditions was approximately 0.8; in the absence of either of these treatments, channel openings were not observed. Glyburide produced a reversible inhibition of the channels activated by cromakalim and energy-depleting conditions. These data provide additional support for the existence of ATP-sensitive K+ channels in central neurons and indicate that the K+ channels whose opening is stimulated by cromakalim are likely to be of the ATP-sensitive type.
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PMID:Glyburide-sensitive K+ channels in cultured rat hippocampal neurons: activation by cromakalim and energy-depleting conditions. 171 18

A widespread defense strategy used by hypoxia-tolerant animals is metabolic depression. One possible mechanism for metabolic depression is "channel arrest." This hypothesis predicts that ion leakage through plasma membrane leakage channels is reduced during an anoxic episode. The decreased ion flux would result in the conservation of energy through the reduction of ATP-demanding ion pumping. We tested this hypothesis with the anoxia-tolerant turtle (Chrysemys picta) as a model system. With intracellular recording used in cortical slices, whole cell input resistance and specific membrane resistivity were monitored under control and anoxic conditions. There were no significant changes in resistance, indicating that the channel arrest defense mechanism was not utilized for energy conservation during short-term anoxia (less than or equal to 120 min).
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PMID:Channel arrest: implications from membrane resistance in turtle neurons. 171 28

Some animal or plant toxins and man-made drugs exert agonist activity on Na+, Ca2+ and K+ channels. The increase in current through these channels is essentially due to an increase of 'open probability' and not of single channel conductance. The enhanced open probability is caused by a prolongation of the open time. In the case of voltage-operated channels this change in open time can be accompanied by increased reopenings and thus slowing of inactivation, or a shift in the activation process to more negative potentials. In the case of the ligand-operated K+ channel, a decrease in the affinity for the normal physiological ligand, ATP, is the mechanism underlying the enhancement of open probability. Agonists show potential clinical applications for Na+ and Ca2+ channels more specifically as positive inotropic agents in cardiac tissue. For K+ channels, the potential therapeutic field is even broader and spans from relaxation of smooth muscle (hypertension, asthma, bladder, uterus), reduction in excitability (arrhythmias, certain skeletal muscle myopathies) to inhibition of neurotransmitter release (depression, epilepsy).
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PMID:Ion channel agonists: expectations for therapy. 172 54

Endothelium-dependent relaxations are depressed in hypertension. In this study we investigated the possible involvement of endothelium-dependent smooth muscle hyperpolarization in this phenomenon. In isolated aortic segments from control rats, acetylcholine (10(-8)-10(-5) M) elicits relaxations after precontraction with norepinephrine (10(-7) M), and acetylcholine or carbachol (10(-5) M) induce smooth muscle hyperpolarization (10.6 +/- 0.9 mV). Both effects disappear after removal of the endothelium and are depressed by tetraethylammonium (3 x 10(-3) M), a rather nonspecific blocker of K+ channels, but not by glibenclamide (10(-5) M), a potent blocker of the ATP-regulated K+ channels, which has a marked effect on the relaxation induced by BRL 38227. The relaxation effect of acetylcholine is impaired in norepinephrine-contracted preparations from hypertensive rats but is not further depressed by tetraethylammonium. In aorta from hypertensive rats, hyperpolarization induced by carbachol was significantly reduced to a mean of only 21.8% of the values obtained in preparations from normotensive rats. From the relaxation-hyperpolarization relation obtained with BRL 38227 (opening K+ channels), it is derived that the endothelium-dependent hyperpolarization (approximately 10 mV) contributes for at least 20-30% of the maximal relaxation effect of acetylcholine on rat aorta. It is concluded that the diminished endothelium-dependent hyperpolarization may contribute to the depression of the endothelium-dependent relaxation in hypertension.
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PMID:Endothelium-dependent relaxation and hyperpolarization in aorta from control and renal hypertensive rats. 172 81

We studied the effects of angiotensin II during low-flow ischemia and reperfusion using red cell-perfused isovolumic rabbit hearts. Under baseline conditions where coronary perfusion pressure (CPP) was 100 mm Hg and left ventricular end-diastolic pressure (LVEDP) was set at 10 mm Hg, 10(-8) M angiotensin II caused a mild increase in LV developed pressure (+12%) and decrease in coronary flow (-8%). Low-flow ischemia was imposed by reducing CPP to 15 mm Hg for 30 min followed by 30 min of reperfusion. During ischemia, the angiotensin II group showed a gradual further reduction in coronary flow in association with a greater depression of LV developed pressure and increase in LVEDP relative to the no-drug group. To separate the effect of angiotensin II on coronary flow from a direct myocardial effect, the angiotensin II group was compared with an additional no-drug group with a matched progressive reduction in coronary flow during ischemia. In these groups, the ischemic depression of LV developed pressure, myocardial ATP levels, and lactate production were similar. However, the ischemic rise in LVEDP was greater (42.0 +/- 5.4 vs. 19.9 +/- 1.3 mm Hg, P less than 0.01) and recovery was incomplete in the angiotensin II group. These observations suggest that angiotensin II exerts a direct adverse effect on LV diastolic relaxation during low-flow ischemia and recovery.
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PMID:Exacerbation of ischemic dysfunction by angiotensin II in red cell-perfused rabbit hearts. Effects on coronary flow, contractility, and high-energy phosphate metabolism. 173 39


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