Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0344329 (collapse)
 28,634 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purple membrane of Halobacterium halobium acts as a light-driven proton pump, ejecting protons from the cell interior into the medium and generating electrochemical proton gradient across the cell membrane. However, the type response of cells to light as measured with a pH electrode in the medium consists of an initial net inflow of protons which subsides and is then replaced by a net outflow which exponentially approaches a new lower steady state pH level. When the light turned off a small transient acidification occurs before the pH returns to the original dark level. We present experiments suggesting that the initial inflow of protons is triggered by the beginning ejection of protons through the purple membrane and that the initial inflow rate is larger than the continuing light-driven outflow. When the initial inflow has decreased exponentially to a small value, the outflow dominates and causes the net acidification of the medium. The initial inflow is apparently driven by a pre-existing electrochemical gradient across the membrane, which the cells can maintain for extended times in the absence of light and oxygen. Treatments which collapse this gradient such as addition of small concentrations of uncouplers abolish the initial inflow. The triggered inflow occurs through the ATPase and is accompanied by ATP synthesis. Inhibitors of the ATPase such as N,N'-dicyclohexylcarbodiimide (DCCD) inhibit ATP synthesis and abolish the inflow. They also abolish the transient light-off acidification, which is apparently caused by a short burst of ATP hydrolysis before the enzyme is blocked by its endogenous inhibitor. Similar transient inflows and outflows of protons are also observed when anaerobic cells are exposed to short oxygen pulses.
 ...
PMID:Light-driven proton translocations in Halobacterium halobium. 0 22

H(+)/site, charge/site, and ATP/site ratios have been determined at coupling sites I, II, and III. Three e(-) donors have been used for coupling site III: ferrocyanide, ascorbate + tetramethyl-p-phenylenediamine (TMPD), and succinate + TMPD. The H(+)/site ratios are 4.0 with ferrocyanide and 6.0 with succinate + TMPD (at pH <7.0); the charge/site ratios are 6.0 with ferrocyanide and with succinate + TMPD (at pH <7.0) and 4.0 with ascorbate + TMPD; the ATP/site ratio is 1.34 with ascorbate + ferrocyanide. These ratios have been obtained in the presence of amounts of antimycin A that provide full inhibition of site II. For coupling sites I and II, ferricyanide has been used as e(-) acceptor and succinate or NAD-linked substrates as e(-) donors. The H(+)/site ratios are 4.0 at sites I and II; the charge/site ratios are 4.0 at site I and 2.0 at site II; the ATP/site ratios are 1.0 at site I and 0.5 at site II. Two major factors affect the stoichiometries: (i) dimension of [unk](H) and (ii) supply of H(+) from the matrix. There is a correlation between collapse of [unk](H) and increase of H(+)/site and charge/site ratios. This indicates that approximation of the phenomenologic stoichiometry of the H(+) pump is obtained when flow ratios are measured at level flow. That charge/site and ATP/site ratios increase when ferrocyanide is e(-) donor and decrease when ferricyanide is e(-) acceptor is attributed to the localization of the redox couple. This leads to separation of 1 charge/e(-) when ferrocyanide is e(-) donor and to consumption of 1 charge/e(-) when ferricyanide is e(-) acceptor. To account for an extrusion of H(+) in excess of that predicted by the loop model, it is proposed that each coupling site contains a channel acting as a H(+) pump.
 ...
PMID:H+/site, charge/site, and ATP/site ratios in mitochondrial electron transport. 3 12

Expiratory-related neurons have been classified according to their phase relation within the respiratory cycle, their response to lung distension and collapse (alpha- and beta-type), and to hyperventilation (tonic firing denoted by "+", cessation of activity by "-"). The dorsal surface of the medulla oblongata was superfused with a metabolite-containing CSF solution and the activity of expiratory (E) and inspiratory-expiratory (IE) neurons was extracellulary recorded. The neuronal sub-types established by their functional behaviour could equally be distinguished by their differential response to one or several metabolites. In contrast to inspiratory (I) neurons, Ealpha- Ebeta-, Ebeta- and IEbeta- neurons are inhibited by 3.5 mM AMP, but are activated by 10 mM citrate (with the exception of Ebeta+ units). Furthermore I cells are activated by ATP, while Ealpha and Ebeta units become inhibited. Vagotomy in some instances affected the response of some IEbeta units. An increase in spike density of IEbeta+ and Ealpha- cells is paralleled by a reduction of both the respiratory rate and the tidal volume, while a lower spike density in IEbeta+, IEbeta- and Ealpha- units is accompanied by increases in respiratory rate and tidal volume. In the case of Ebeta+ and Ebeta- cells lower activity is associated with an increased tidal volume. No metabolite-induced changes could be obtained with cardiovascular or unspecific reticular neurons.
 ...
PMID:Metabolic control of respiratory neuronal activity and the accompanying changey-expiratory neurons. 18 81

The effect of the transmembrane potential (delta psi) and the proton concentration gradient (delta pH) across the chromaffin granule membrane upon the rate and extent of catecholamine accumulation was studied in isolated bovine chromaffin granules. Freshly isolated chromaffin granules had an intragranular pH of 5.5 as measured by [14C]methylamine distribution. The addition of ATP to a suspension of granules resulted in the generation of a membrane potential, positive inside, as measured by [14C]thiocyanate (SCN-) distribution. The addition of carboxyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP), a proton translocator, resulted in a reversal of the potential to negative values (measured by [3H]tetramethylphenylphosphonium (TPMP+)) approaching -90 mV. Changing the external pH of a granular suspension incubated with FCCP produced a linear perturbation in the measured potential from positive to negative values, which can be explained by the distribution of protons according to their electrochemical gradient. When ammonia (1 to 50 mM) was added to highly buffered suspensions of chromaffin granules there was a dose-dependent decrease in the transmembrane proton gradient (delta pH) and an increase in the membrane potential (delta psi). On the other hand, thiocyanate or FCCP, at varying concentration, produced a dose-related collapse of the membrane potential and had no effect upon the transmembrane proton gradient. The addition of larger concentrations of catecholamines caused a decrease in the transmembrane proton gradient and an increase in the membrane potential. Time-resolved influx of catecholamines into the granules was studied radiochemically using low external catecholamine concentrations. The accumulation of epinephrine or norepinephrine was over one order of magnitude greater in the presence of ATP than in its absence. The rate and extent of amine accumulation was found to be related to the magnitude of the membrane potential at fixed transmembrane proton concentration (delta pH) values. Likewise, the accumulation was related to the magnitude of the delta pH at fixed membrane potential values. These results suggest that the existence of both a transmembrane proton gradient and a membrane potential are required for optimal catecholamine accumulation to occur.
 ...
PMID:Protonmotive force and catecholamine transport in isolated chromaffin granules. 43 57

1. From electron micrographs of chromatophores from Rhodopseudomonas spaeroides and from the estimated bacteriochlorophyll per chromatophore was estimated. The mean diameter of the chromatophore vesicles was 600 A. 2. The decay of the flash-induced electric potential across the chromatophore membrane measured by the carotenoid band shift was 20% accelerated by about one valinomycin molecule per 4700 bacteriochlorophyll, i.e. by one ionophore molecule per chromatophore. 3. The inhibition of the flash-induced ATP formation by valinomycin followed a similar pattern to the accelerated decay of the electric potential. 4. The single turnover flash yield of ATP synthesis gave a mean value of one ATP per 1470 bacteriochlorophyll or about 3 ATP per vesicle. 5. With regard to the partitioning of the ionophore between the membrane (85%) and aqueous phase (15%) we conclude that one molecule of valinomycin per chromatophore is sufficient to begin to collapse the electrical potential and inhibit ATP synthesis. It is therefore suggested that the membrane potential is an essential component of the energized state which is used for phosphorylation. The results correspond to those obtained for the 100-fold larger vesicles in chloroplasts (thylakoids) where one molecule of ioophore is also sufficient to quench both events.
 ...
PMID:The functional unit of electrical events and phosphorylation in chromatophores from Rhodopseudomonas sphaeroides. 108 Jun 74

Stimulation with extracellular ATP causes a rapid initial transient rise followed by asynchronous periodic oscillations in cytosolic calcium ion activity ([Ca2+]i) in individual aortic smooth muscle cells in either HEPES-buffered or HCO3(-)-buffered saline. The dose at which one-half of the cells display an initial rise in cytosolic calcium is 0.11 microM ATP in the presence of external Ca2+ and 0.88 microM ATP in the absence of external Ca2+; the corresponding value for oscillations in the presence of external Ca2+ is 2.6 microM ATP. While the initial transient displays rapid desensitization, the oscillations persist for greater than 30 min in the continuous presence of ATP. The presence of the agonist ATP is also absolutely required for the maintenance of the oscillations, presumably to provide continuous activation of P2 purinoceptors. The average frequency of oscillation is approximately 0.9 min-1. The frequency depends only slightly on the concentration of ATP, and oscillations do not collapse into a prolonged elevated [Ca2+]i at high concentrations of ATP. Both Ca2+ influx and release from internal stores participate in the initial transient. Oscillations are not produced in the absence of external Ca2+ but are initiated upon the addition of external Ca2+ in the continued presence of ATP. Oscillations in progress are abolished by the removal of extracellular Ca2+ with one additional peak occurring after the Ca2+ removal. These data suggest that extracellular Ca2+ influx is required for the maintenance of the posttransient oscillations, presumably to provide the Ca2+ necessary for refilling intracellular Ca2+ pools that are the source of the oscillating [Ca2+]i. The Ca2+ influx is not regulated by voltage-gated Ca2+ channels. The data in this report are consistent with the view that the initial transient has contributions from two receptor-mediated pathways, and the oscillations are controlled either by a mechanism separate from the ones that control the initial transient or by steps whose control diverges before the point of desensitization.
 ...
PMID:Independent pathways regulate the cytosolic [Ca2+] initial transient and subsequent oscillations in individual cultured arterial smooth muscle cells responding to extracellular ATP. 131 42

There is increasing evidence that the calcium ion plays a critical role in both toxic cell killing and programmed cell death. Thus, in a variety of experimental systems a perturbation of intracellular Ca2+ homeostasis due to increased Ca2+ influx and/or inhibition of Ca2+ extrusion has been found to be an early event in the development of cell injury. It is clear that sustained increases in intracellular Ca2+ can activate cytotoxic mechanisms which result in perturbations of cellular structure and function. For example, the stimulation of Ca(2+)-dependent proteases can result in a disruption of cytoskeletal organization and the formation of surface protrusions (blebs) and Ca(2+)-mediated phospholipase activation can result in an impairment of mitochondrial function with collapse of membrane potential and cessation of ATP synthesis. The activation of a Ca2+, Mg(2+)-dependent nuclear endonuclease is associated with chromatin cleavage and appears to play a crucial role in programmed cell death (apoptosis) in the immune system and other tissues. There is also recent evidence that this process may be responsible for the immunotoxicity of dioxins and organotin compounds and involved in the killing of adenocarcinoma cells by tumor necrosis factor alpha. Although calcium ions appear to be required for endonuclease activity during apoptosis, this process is also influenced by other factors, e.g. protein kinase C activity, intracellular polyamine and Zn2+ levels, chromatin structure, etc. Thus, the regulation of endonuclease activity under both physiological and toxicological conditions appears to be complex and to involve multiple factors.
 ...
PMID:Ca(2+)-dependent mechanisms of cytotoxicity and programmed cell death. 133 78

The presence of chloride conductance in basolateral membranes of proximal tubule is controversial. We measured 36Cl uptake in basolateral membranes loaded with KCl and suspended in a K(+)-free solution to create a positive intravesicular potential difference. Under these conditions, 36Cl uptake was maximal at 1 min, remained stable for at least 10 min and decreased to equilibrium levels by 60-120 min. Collapse of the voltage by valinomycin decreased 36Cl uptake by 46%, indicating the presence of K(+)-gradient-dependent chloride uptake. The chloride channel inhibitor diphenylamine-2-carboxylic acid inhibited 36Cl uptake in a dose-dependent fashion. 36Cl uptake was inhibited equally by unlabeled chloride, iodide and nitrate but not by sulfate or gluconate, indicating that the basolateral anion conductance is relatively selective. 36Cl uptake was pH independent but was calcium dependent. Phosphorylation of basolateral membranes with ATP significantly decreased 36Cl uptake, but the inhibitory effect of ATP was not further altered by exogenous cyclic AMP or the active phorbol ester PMA. These data demonstrate the presence of a relatively selective basolateral anion conductance which is regulated by pH, calcium and ATP.
 ...
PMID:Anion channel in basolateral cortical membranes of the rabbit kidney. 133 46

The permeabilization of Trypanosoma brucei procyclic and bloodstream trypomastigotes with digitonin permitted the quantitative estimation of a mitochondrial membrane potential of the order of 130-140 mV, in both forms, using safranine O. Dependence on substrate oxidation and response of the procyclic mitochondrial membrane potential to phosphate, FCCP, valinomycin, and Ca2+ indicate that these mitochondria behave similarly to vertebrate mitochondria regarding the properties of their electrochemical proton gradient. In contrast, in bloodstream mitochondria, development of a membrane potential was independent of substrate oxidation and dependent on hydrolysis of ATP by the mitochondrial oligomycin-sensitive ATPase, as demonstrated by collapse of the membrane potential by oligomycin and its insensitivity to the respiratory chain-inhibitor antimycin A. Mitochondria of T. brucei bloodstream forms were also able to take up Ca2+ by an electrophoretic mechanism. This is the first report of the presence of a Ca2+ transport mechanism in an eukaryotic cell devoid of complete tricarboxylic acid cycle and respiratory chain, the activities of which are known to be regulated by changes in intramitochondrial calcium concentration in other cells.
 ...
PMID:Energization-dependent Ca2+ accumulation in Trypanosoma brucei bloodstream and procyclic trypomastigotes mitochondria. 148 49

The impacts of energy-yielding substrates on coronary flow autoregulation, cytoplasmic phosphorylation potential ([ATP]/([ADP][Pi])] and purine nucleoside production were studied in Langendorff-perfused guinea pig hearts. The perfusion medium was substrate-free or contained glucose alone or in combination with pyruvate, lactate, acetate, or octanoate as fatty acid. When coronary flow was adjusted for myocardial oxygen consumption, only pyruvate supported near-perfect intrinsic autoregulation at highly sustained [ATP]/([ADP][Pi]) and low interstitial adenosine concentrations ([Ado]). In contrast, hearts perfused with substrate-free medium were deenergized at very high [Ado], especially at supraphysiological pressures, which markedly impaired auto-regulatory vasoconstriction. Thus, efficient autoregulatory vasoconstriction was associated with high [ATP]/([ADP][Pi]) at low [Ado]. On the other hand, autoregulatory vasodilation at subphysiological pressures was associated with increased [Ado] and partially blocked by 28 microM theophylline demonstrating (partial) adenosine mediation. Massive accumulation of IMP, especially relative to free cytoplasmic AMP, occurred at normal intracellular pH during myocyte deenergization by substrate-free perfusion. This may indicate allosteric activation of native AMP deaminase in situ, perhaps because of collapse of [ATP]/([ADP][Pi]). Similarly, rates of adenosine plus inosine release and of total purines, also including urate, exhibited non-linear sigmoidal rather than linear or rectangular hyperbolic dependences on free cytoplasmic AMP concentration (not total AMP content). Since inclusion of IMP as a co-variable of free AMP appreciably improved the sigmoidal fits, IMP appeared to be a significant precursor of released inosine in guinea pig heart.
 ...
PMID:Coronary autoregulation and purine release in normoxic heart at various cytoplasmic phosphorylation potentials: disparate effects of adenosine. 152 16


1 2 3 4 5 6 7 8 9 10 Next >>