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

Lowering myocardial temperature increases contractile force, presumably by increasing intracellular calcium content. To study the mechanisms behind this, we compared the effects of some known inotropic interventions with hypothermia on mechanical restitution and post-rest contractile force in isolated guinea-pig papillary muscles. In four groups (n = 6 per group), the effects of: (1) reducing the ability for Na/Ca exchange to extrude Ca2+ (a) by increasing [Na+]i with ouabain or (b) by increasing [Ca2+]o; and (2) activation of calcium channels with Bay-K 8644, were compared with lowering temperature from 37 to 27 degrees C. Normally (at 37 degrees C and 2 mM CaCl2), mechanical restitution could be described by a rapid recovery phase with a time constant between 180 and 220 ms, followed by a slowly decaying phase with a time constant between 5000 and 8000 ms and post-rest contractions (1-10 min rest) were markedly depressed compared to steady-state contractions. Steady-state developed force was markedly increased at 27 degrees C, after 1 microM ouabain, 6 mM CaCl2 or 0.1 microM Bay-K 8644. At 27 degrees C the rapid recovery phase of restitution was delayed while the slowly decaying phase was not affected. Ouabain and increased [Ca2+]o caused elevation of the slowly decaying phase of restitution and markedly attenuated the post-rest depression of developed force, which may be attributed to a reduced diastolic extrusion of Ca2+ via the Na/Ca exchanger. Hypothermia and Bay-K 8644 on the other hand, augmented this post-rest depression. Hence, this study suggests that increased Ca2+ influx due to delayed inactivation of calcium channels may account for the increased developed force during hypothermia rather than reduced diastolic extrusion of Ca2+ via the Na/Ca exchanger.
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PMID:Mechanisms for hypothermia-induced increase in contractile force studied by mechanical restitution and post-rest contractions in guinea-pig papillary muscle. 769 97

Effective mechanisms of matrine (Mat) in contraction were observed in isolated rat vasa deferens. Mat caused a strong concentration-dependent contraction of vasa deferens, and this contraction was competitively inhibited by prazosin (Pra, 10 mumol.L-1) and nifedipine (Nif, 50 nmol.L-1), with depression of maximal responses. Their pA2 value was 5.1 and 9.29, respectively. The contraction was also inhibited by verapamil (Ver, 1 mumol.L-1) with depression of maximal responses; but this antagonism was noncompetitive. Its pD2 value was 6.07. Mat promoted CaCl2-induced contraction of vas deferens. The effect of Mat was enhanced in proportion to increase in concentrations of CaCl2. Mat markedly strengthened KCl-induced contraction of vas deferens. The results suggest that one of the mechanisms of the contractive effects of Mat within a certain range of concentrations was related to the activation of the calcium channel.
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PMID:[Relation of effects of matrine on rat vasa deferens to activation of calcium channels]. 797 88

1. Previous work has suggested that presynaptic effects of adenosine may be dependent on divalent cations. The present study was undertaken to determine whether a similar requirement existed at postsynaptic sites. 2. Extracellular recordings were made in the CA1 pyramidal cell layer of rat hippocampal slices following orthodromic stimulation of Schaffer collateral fibres in stratum radiatum or antidromic stimulation of the alveus. In antidromic stimulation experiments, CaCl2 was omitted (calcium-free medium) or reduced to 0.24 mM (low calcium medium) and in some experiments MgSO4 was increased to 2 mM. Kynurenic acid at concentrations of 1 and 5 mM in calcium-free medium and 1 mM in low calcium medium had no effect on secondary spike size. 3. Adenosine and baclofen induced a concentration-dependent reduction in the amplitude of orthodromic potentials with maximum effects at 20 and 5 microM respectively. 4. In nominally calcium-free medium, bursts of multiple population spikes were obtained in response to antidromic stimulation. Adenosine had little effect in reducing the secondary spike amplitude. At high concentration (2 mM) an initial depression was seen which declined within 3-5 min. 5. Sensitivity to adenosine was restored in low calcium medium or by raising magnesium. Although raising the divalent cation concentration increased the inhibitory effect of adenosine, desensitization was still seen. 6. 2-Chloroadenosine (100-500 microM) and R-PIA (50 microM), which are not substrates for either the nucleoside transporters or adenosine deaminase, were inactive in the absence of calcium. S-(2-hydroxy-5 nitrobenzyl)-6-thioinosine, an adenosine uptake blocker, at a concentration 100 MicroM had no effect on secondary potential size and did not restore adenosine sensitivity in calcium-free medium.7. Thapsigargin, which discharges intracellular calcium stores, had no significant effect at 1 MicroM on the bursts of action potentials and did not change the effect of 0.5 mM adenosine in calcium-free medium.8. Unlike adenosine, baclofen concentration-dependently reduced the secondary spike size in calcium free medium and no sign of recovery was observed during maintained superfusion for up to 45 min. No cross-desensitization was seen between baclofen and adenosine.9. Applications of adenosine locally by pressure to neuronal somata or dendrites still resulted in desensitized responses in calcium-free medium.10. It is concluded that the postsynaptic sensitivity to adenosine is dependent on the concentration of divalent cations in the extracellular space implying an effect of cations on adenosine receptor activation or transduction processes.
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PMID:The effect of calcium removal on the suppression by adenosine of epileptiform activity in the hippocampus: demonstration of desensitization. 803 57

We have studied several effects of hydralazine in the bisected rat vas deferens. Hydralazine produced a shift to the left of the concentration-response curve for noradrenaline, with potentiation of the maximal response in both portions of the vas deferens. In contrast it caused a shift to the right of the concentration-response curve for noradrenaline in preparations pretreated with cocaine (inhibitor of catecholamine neuronal uptake), and of the curve for methoxamine and for CaCl2 (in depolarizing medium with K+ 55 mM), in all cases with depression of the maximal response. Hydralazine enhanced the contractions induced by noradrenaline in Ca(2+)-free medium, except in the presence of cocaine. It had no effect on [3H]noradrenaline neuronal uptake into noradrenergic neurons of the vas deferens, nor did it affect basal or K(+)-induced 45Ca2+ uptake. These results suggest that hydralazine potentiates the contractions elicited by noradrenaline by a mechanism other than blockade of the neuronal uptake of this catecholamine. Our results also suggest that the inhibition by hydralazine of the contractions elicited by Ca2+ (in Ca(2+)-free depolarizing high-K+ 55 mM solution) and by methoxamine is not due to an action on voltage-dependent Ca2+ channels, but may reflect an intracellular site of action.
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PMID:Pharmacological study of several effects of hydralazine in the bisected rat vas deferens. 813 73

Previously the plasma membrane-bound or purified Ca(2+)-translocation ATPase (Ca2+ pump) was found to be activated and phosphorylated by protein kinase C in vitro (K. K. W. Wang et al. 1991, J. Biol. Chem. 266, 9078-9085). We now show that in intact human erythrocytes phorbol-12-myristate 13-acetate (PMA), a known stimulator of protein kinase C, decreases the amplitude of the intracellular calcium ([Ca2+]i) transient induced by 2.5 microM CaCl2 and 10 microM A23187. Since PMA did not affect Ca2+ influx, the decrease in amplitude was most likely due to the stimulation of the Ca2+ pump, the major mechanism of calcium extrusion in these cells. The effect was dose-dependent, the maximum decrease in amplitude (33%) occurring at 1 microM PMA. The depression of the [Ca2+]i transient was further enhanced by the phosphatase inhibitor okadaic acid. It was reversed by the protein kinase C inhibitor staurosporine and could not be mimicked by inactive PMA analogues. In erythrocytes labeled with [32P]orthophosphate, PMA treatment phosphorylated the Ca(2+)-ATPase in a dose-dependent manner. The phosphorylation was inhibited by staurosporine and was slightly enhanced by okadaic acid. Changes in lipid phosphorylation and content were studied under the same conditions in intact cells. The turnover of 32P and lipid phosphate in phosphatidylinositol 4,5-bisphosphate (PIP2) was inhibited by 1 mM adriamycin, concomitant with an increased amplitude of the [Ca2+]i transient. The PIP2 content and its 32P radioactive did not, however, change with PMA stimulation. We conclude that while both protein kinase C and polyphosphoinositides are regulators of Ca(2+)-ATPase activity in the intact human erythrocyte, stimulation of the enzyme activity by PMA is predominantly protein kinase C-mediated.
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PMID:Regulation of the activity and phosphorylation of the plasma membrane Ca(2+)-ATPase by protein kinase C in intact human erythrocytes. 821 16

The effects of the thiadiazinone derivative, 5-[1-(3,4-dimethoxybenzoyl)-1,2,3,4-tetrahydrochinolin-6-yl]-6-met hyl-3,6- dihydro-2H-1,3,4-thiadiazin-2-on (EMD 53998), and of its (+)EMD 57033 and (-)EMD 57439 enantiomers, were tested on the contractile properties and cytosolic [Ca2+] ([Ca2+]i) transients of single intact guinea pig cardiac myocytes. Cells were loaded with the ester form of the fluorescent probe, indo-1, and bathed in a N-2-hydroxyethyl-piperazine-N'-2-ethanesulfonic acid-buffered solution at 25 degrees C (1 mM of CaCl2, 1 Hz stimulation rate). All three substances exerted a pronounced increase in twitch amplitude: the maximal effect of the racemate (380% of control value) was approximately the sum of the effects of its two enantiomers (186 and 236% of control value for the (+)- and (-)-enantiomer, respectively). The [Ca2+]i transient, measured as the 410-to-490 nm indo-1 fluorescence ratio transient after excitation, was increased by the racemate and its (-)-enantiomer (172 and 152% of control value, respectively), but was not increased by the (+)-enantiomer. The racemate and the (-)-enantiomer, but not the (+)-enantiomer, markedly reduced the contraction duration and [Ca2+]i transient duration. In unstimulated cells resting length was significantly reduced by the (+)-enantiomer, and this was accompanied by a decrease in indo-1 fluorescence; the (-)-enantiomer had no effect on either parameter. In the presence of 2,3 butanedione monoxime (BDM), which markedly reduces twitch amplitude by inhibiting cross-bridge mechanics, addition of the (+)-enantiomer restored the twitch contraction to above the pre-BDM level without augmenting the [Ca2+]i transient. In contrast, the (-)-enantiomer failed to reverse the BDM-induced contractile depression, even though it caused a significant increase of the [Ca2+]i transient. Thus, in intact cells the positive inotropic effect of EMD 53998 is due to specific properties of its enantiomers: the (-)-enantiomer has adenosine 3',5'-cyclic monophosphate-like effects (increase in amplitude and reduction of [Ca2+]i transient and contraction durations), whereas the (+)-enantiomer enhances the myofilament-Ca2+ interaction.
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PMID:Enantiomeric dissection of the effects of the inotropic agent, EMD 53998, in single cardiac myocytes. 838 21

Acetaldehyde (ACA), an ethanol metabolite, exerts both stimulatory and depressive effects on isolated myocardial tissue, but its impact on individual cardiac myocytes is unknown. The purpose of this study was to determine whether ACA-induced myocardial depression is due to an intrinsic alteration of the contractile properties of heart at the cellular level. Mechanical properties of adult rat ventricular myocytes were evaluated using a video edge-detection system. Myocytes were electrically stimulated to contract at 0.5 Hz under isotonic conditions in a physiological buffer containing 1 mM CaCl2. Contractile properties analyzed include: peak twitch amplitude (PTA), time-to-PTA (TPT), time-to-relengthening (TR90) and maximal velocities of shortening and relengthening (+/-dL/dt). Ca2+ transients were measured as fura-2 fluorescence intensity (FFI) changes. ACA (1-30 mM) disproportionately depressed PTA and FFI in a dose-dependent manner, with maximal inhibitions of 57 and 19%, respectively. Neither the durations nor maximal velocities of shortening and relengthening were affected by ACA. The depression of cell shortening by ACA was either attenuated or blocked by BayK 8644 or elevated extracellular Ca2+ (2.7 mM). In addition, ACA also reduced caffeine-induced FFI changes. These results suggest that ACA-induced myocardial depression in multicellular preparations is due to an intrinsic action on individual myocytes. The mechanism underlying ACA-induced myocardial depression may be due, in part, to either reduced Ca2+ entry through voltage-dependent Ca2+ channels and/or depression of sarcoplasmic reticular Ca2+ release.
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PMID:Acetaldehyde depresses shortening and intracellular Ca2+ transients in adult rat ventricular myocytes. 935 29

Using patch-clamp techniques we studied several aspects of intracellular GABA(A) and glycine Cl- current regulation in cortical and spinal cord neurons, respectively. Activation of PKA with a permeable analog of cyclic AMP (cAMP) produced a potentiation of the Cl- current activated with glycine, but not of the current induced with GABA. The inactive analog was without effect. Activation of PKC with 1 microM PMA reduced the amplitude of the GABA(A) and glycine currents. Internal application of 1 mM cGMP, on the other hand, had no effect on the amplitude of either current. The amplitude of these inhibitory currents changed slightly during 20 min of patch-clamp recording. Internal perfusion of the neurons with 1 microM okadaic acid, a phosphatase inhibitor, induced potentiation in both currents. The amplitude of GABA(A) and glycine currents recorded with 1 mM internal CaCl2 and 10 mM EGTA (10 nM free Ca2+) decayed by less than 30% of control. Increasing the CaCl2 concentration to 10 mM (34 microM free Ca2+) induced a transient potentiation of the GABA(A) current. A strong depression of current amplitude was found with longer times of dialysis. The glycine current, on the contrary, was unchanged by increasing the intracellular Ca2+ concentration. Activation of G proteins with internal FAl4- induced an inhibition of the GABA(A) current, but potentiated the amplitude of the strychnine-sensitive Cl- current. These results indicate that GABA(A) and glycine receptors are differentially regulated by activation of protein kinases, G proteins and Ca2+. This conclusion supports the existence of selectivity in the intracellular regulation of these two receptor types.
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PMID:Differential intracellular regulation of cortical GABA(A) and spinal glycine receptors in cultured neurons. 937 87

Tissues of mouse diaphragms were incubated in Liley solution containing 2, 4, 6 and 10 mmol/l calcium. When diaphragm tissue was incubated in 10 mmol/l calcium, an increase of intracellular calcium concentration from 314 +/- 28 to 637 +/- 26 nmol/l was estimated by fluorescent Ca2+ indicator Fura-2/AM. Moreover, incubation of the tissue in 10 mmol/l Ca2+ led to complete inhibition of electrogenic activity of the sodium pump, as measured by intracellular microelectrodes in a single muscle cell. This inhibition was fully reversible after 5 min washing with Liley solution containing 2 mmol/l CaCl2. The Ca(2+)-induced blocking effect on electrogenic activity of the sodium pump was accompanied by inhibition of glucose incorporation into the muscle tissue. Calcium at concentrations of 6 and 10 mmol/l in bath medium significantly inhibited both CO2 production and O2 consumption. A continual decrease of respiration (CO2/O2) quotient was observed under increasing concentrations of calcium. Moreover, an exponential decrease of ATP tissue levels was observed at increasing concentrations of calcium in the bath medium. On the other hand, massive acceleration of anaerobic glycolysis induced by incubation of the tissue in a medium containing high calcium concentration is improbable. This may be deduced from the fact that only about an 50% increase of lactate content in muscle tissue was observed when diaphragms were incubated for 30 min in medium containing calcium ions at 6 and 10 mmol/l as compared with the control tissue incubated for the same time in the medium containing 2 mmol/l CaCl2. In conclusion it could be stressed that increase of Ca2+ concentration in bath medium induced in diaphragm muscle tissue an elevation of intracellular Ca2+ concentration accompanied by a depression of sodium pump electrogenic activity and a depression of energy metabolism. These changes may be involved in pathology of muscle tissue during the Ca2+ overload.
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PMID:Ca(2+)-induced inhibition of sodium pump: effects on energetic metabolism of mouse diaphragm tissue. 983 48

Sepsis is a major cause of death in intensive care units. Clinically, sepsis induces a number of physiologic and metabolic abnormalities, including decreased myocardial contractility and decreased plasma ionized calcium. There is debate about the proper therapy of hypocalcemia in sepsis because calcium administration may worsen cell function by causing intracellular Ca2+ overload. We investigated the effect of Ca2+ administration on myocardial systolic and diastolic function in an extensively utilized rat model of sepsis, i.e., the cecal ligation and puncture model (CLP). Approximately 24 h after CLP or sham surgery, rats were anesthetized and myocardial function assessed in vivo by a left ventricular Millar catheter and simultaneous two-dimensional guided M-mode echocardiography. Septic rats had a 28% decrease in peak left ventricular developed pressure, a 30% decrease in +dP/ dt, and a 23% decrease in -dP/dt (p < 0.05). Plasma ionized Ca2+ was decreased in septic compared with that in sham rats: 4.9 +/- 0.9 and 5.6 +/- 0.01 mg/dl, respectively (p < 0.05). CaCl2 improved both systolic and diastolic function and there was no evidence of adverse effects of Ca2+ even at supraphysiologic levels. Surprisingly, correction of decreased afterload in septic rats, using the pure alpha-agonist phenylephrine, caused normalization of all indices of cardiac contractility, indicating that the presumed decrease in cardiac function was due entirely to an effect of the decreased afterload to "unload" the left ventricle. We conclude that Ca2+ administration is not detrimental to cardiac function in the rat CLP model. Although the rat CLP model is widely utilized and reproduces many of the clinical hallmarks of sepsis, it does not cause intrinsic myocardial depression and, therefore, it may not be an appropriate model to investigate the clinical cardiac dysfunction that occurs in patients with sepsis.
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PMID:Reversal of hypocalcemia and decreased afterload in sepsis. Effect on myocardial systolic and diastolic function. 984 97


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