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Biomedical subjects

E J Harris

Publications and source records attributed to E J Harris.

At least 127 records · Page 7Linked to original sources
PubMed1968

The dependence on dicarboxylic acids and energy of citrate accumulation in depleted rat liver mitochondria.

The accumulation of some organic anions in the space inaccessible to sucrose of rat liver mitochondria was measured. In untreated mitochondria anions were apparently concentrated from 1mm applied concentration by between five- and 22-fold, depending on their charge. After depletion of endogenous reserves either with uncoupling agent or with oligomycin uptakes were decreased. The accumulation of citrate was restored by combinations of a dicarboxylic acid (malate, succinate, maleate or meso-tartrate) and energy. The energy could either be provided by oxidation of a suitable dicarboxylic acid or from ascorbate in the presence of tetramethylphenylenediamine, or from ATP. The restoration of citrate uptake is not necessarily accompanied by a gain of K(+), but a cation- and energy-linked citrate uptake can be induced with valinomycin. When citrate is added to mitochondria in the presence of malate the latter is competitively displaced. The anion accumulation could arise from an internal energy-linked positive potential.

Adenosine Triphosphate↗
PubMed1967

Decreased K+ conductance produced by Ba++ in frog sartorius fibers.

The action of Ba(++) on membrane potential (E(m)) and resistance (R(m)) of frog (R. pipiens) sartorius fibers was studied. In normal Cl(-) Ringer's, Ba(++) (<9 mM) did not depolarize or induce contractions, but increased R(m) slightly above the control value of 3.8 +/- 0.6 K ohm-cm(2). In Cl(-)-free Ringer's (methane sulfonate) R(m) was 28.8 +/- 2.8 K ohm-cm(2), and low concentrations of Ba(++) (0.05-5.0 mM) depolarized and induced spontaneous contractions (fibrillation), even in tetrodotoxin. To stop disturbance of the microelectrodes, contractions were prevented by using two Cl(-)-free solutions: (a) twice hypertonic with sucrose (230 mM), or (b) high K(+) (83 mM) partially replacing Na(+). In the hypertonic solution, the fiber diameters decreased, E(m) increased slightly, and R(m) decreased to 9.0 +/- 0.6 K ohm-cm(2) (perhaps due to swelling of sarcotubules). Ba(++) (0.5 mM) rapidly increased R(m) to 31.3 +/- 3.8, decreased E(m) (e.g., to -30 mv), and induced spontaneous "action potentials;" Sr(++) had no effect. In the high K(+) solution, the fibers were nearly completely depolarized, and R(m) was decreased markedly to 1.5 +/- 0.2 K ohm-cm(2); Ba(++) increased R(m) to 6.7 +/- 0.5 K ohm-cm(2). The Ba(++) actions usually began within 0.5 min and reached a maximum within 5 min. Addition of SO(4) (=), to precipitate the Ba(++), rapidly reversed the increase in R(m). Ba(++) must act by decreasing K(+) conductance (g(K)). In Cl(-) Ringer's, the high g(Cl)/g(K) ratio masked the effect of Ba(++) on g(K). Thus, small concentrations of Ba(++) specifically and rapidly decrease g(K).

Action Potentials↗
PubMed1967

The stoicheiometry of sodium ion movement from frog muscle.

1. Further measurements of the consumption of high energy phosphate during the active extrusion of sodium ions from frog muscle were made in the presence of iodoacetate or dinitrofluorobenzene.2. In the presence of iodoacetate the consumption of ATP for phosphorylation of hexose is appreciable and so a deduction is made from the total ATP consumption during the ion movement.3. In the presence of dinitrofluorobenzene the deamination of adenosine monophosphate makes the changes in adenosine triphosphate and diphosphate unequal so that both substances have to be measured.4. The present results point to the active movement of between 2.5 and 3 sodium ions per high energy phosphate bond split.

Adenine Nucleotides↗
PubMed1966

Induced and spontaneous movements of potassium ions into mitochondria.

1. Net movements of K(+) into metabolizing liver mitochondria before and after the addition of valinomycin have been measured by using selective glass electrodes. The advantage of using an automatic titrator to hold the K(+) concentration constant is demonstrated. 2. According to the energy source provided the induced movement after the addition of valinomycin can be either in or out. 3. Uptakes and rates of movement are higher in media containing acetate (20mm) than in media containing chloride (20mm). In each mixture comparisons were made at three pH values; at pH6.36 the induced rates are less than at pH7.0 or 7.8 but the final uptakes attained are increased. 4. The rate of uptake is increased by inorganic phosphate. 5. The presence of Mg(2+) slightly decreases the induced uptake and rate of movement; Ca(2+) can cause the induced movement of K(+) to be outward. 6. The rate of induced K(+) movement is related to the rate of extra oxygen consumption but with different factors in acetate (24 K(+) ions/oxygen molecule) and chloride media (10 K(+) ions/oxygen molecule). 7. The amount of K(+) gained is proportional to the loss of fluorescence of the suspension. 8. When K(+) moves there is a contrary movement of H(+) but the ratio depends on the conditions. At pH6.36 in chloride media the K(+)/H(+) ratio exceeded 10:1 and in no case did it fall to unity. 9. When K(+) is taken up there is a proportional diminution of light-scattering; it is inferred that swelling takes place along with K(+) accumulation. 10. It is shown by the use of tracer (42)K(+) that turnover of the ion in mitochondria is increased by valinomycin. 11. It is concluded that valinomycin both increases the permeability to K(+) and also, given an adequate energy supply, stimulates the K(+)-accumulating mechanism.

Adenosine Triphosphatases↗
PubMed1966

The effects of potassium ions and denervation on protein synthesis and the transport of amino acids in muscle.

1. The effects of varying concentrations of K(+) during incubation, of denervation and of various drugs on the accumulation of (14)C-labelled amino acids, their incorporation into protein and the stimulation of these processes by insulin in rat diaphragm preparations were studied. 2. The accumulation of glycine and aminoisobutyrate and incorporation of glycine into protein was less in tissue incubated in K(+)-free buffer or 20mm-K(+) than with 5-10mm-K(+). Incorporation of leucine was unaffected. 3. Incorporation into protein of amino acids by diaphragm that had been denervated 3 days previously was elevated. Accumulation of both glycine and aminoisobutyrate was also raised but that of phenylalanine was unaffected. 4. Accumulation of glycine by diaphragm and extensor digitorum longus muscle was decreased by a number of agents including cocaine and mepyramine. 5. The stimulation of incorporation by insulin was unaffected by changes in K(+) or in the presence of cocaine and mepyramine. Denervated tissue was markedly less responsive to insulin than its control. 6. The results are discussed in the context of the relation of amino acid accumulation to operation of the Na(+) pump and the influence of insulin thereon.

Acetylcholine↗
PubMed1966

Consumption of high-energy phosphates during active sodium and potassium interchange in frog muscle.

1. Potassium-depleted muscles have been analysed for cations, phosphocreatine, adenosine triphosphate and lactate before or after an exposure to a medium with 10 mM potassium salt.2. The net movements of sodium out and potassium in when the system is anaerobic but not otherwise poisoned are accompanied by break-down of phosphocreatine and formation of lactate.3. In bicarbonate media oligomycin has little perceptible effect upon these observed changes, which is taken to indicate that mitochondrial phosphorylation is not essential. An inhibition by oligomycin was noted in media buffered with Tris.4. Dinitrofluorobenzene, which poisons creatine phosphotransferase, leads to the cation changes being accompanied by break-down of ATP and formation of lactate. This indicates that ATP is more directly concerned with energizing the ion movements than is phosphocreatine.5. Iodoacetate inhibits the glycolytic process and the ion movement is then accompanied by more phosphocreatine break-down than in the other conditions; the level of ATP also falls.6. The mean number of sodium ions moved out is closely equal to the number of potassium ions moved in. Conditions mentioned in (2) and (3) above lead to about 2.5 sodium ions being moved out per high-energy phosphate bond hydrolysed provided allowance is made for the glycolytic resynthesis of ATP.7. Some measurements of membrane potential under comparable conditions of ion movement are reported and these are used to calculate the energy requirement of the process of sodium-potassium interchange.

Adenosine Triphosphate↗
PubMed1966

Effects of sodium extrusion and local anaesthetics on muscle membrane resistance and potential.

1. Membrane potentials and resistances of K-depleted muscles were measured in the cold and again after warming in K-containing media so that active ion movements occurred.2. On warming there was a fall of resistance and a gradual rise of potential which passed through a maximum. Later measurements of resistance in a chloride medium showed that values were, if anything, higher than initially in the warm.3. The excess potentials measured approximated to those required to induce passive inward movement of the K ions through the measured K resistance.4. Permeabilities for K(+) and Cl(-) were deduced. When cocaine, procaine, amytal or mepyramine were added or when K(+) was replaced by Rb(+) in the Cl(-)-free solution the K(+) permeability was eventually reduced. The same agents led to an enhanced initial response of potential to warming, but later the potentials in Cl(-)-free media fell to less than the K(+) equilibrium values.5. A method for obtaining the resistivity of the membrane from measurements made in conditions of non-linear voltage-current dependence was applied.

Amobarbital↗