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D McCall

Publications and source records attributed to D McCall.

51 records · Page 3Linked to original sources
PubMed1976

Influence of procainamide on sodium and potassium exchange and permeabilities in cultured human cells.

The effect of procainamide on membrane cation exchange was investigated using monolayer cultures of Girardi heart cells. The initial effect of procainamide (10(-6) to 10(-3) mol/litre) was to produce a prompt reduction of the passive Na influx, dose-dependent along a sigmoid log dose-response curve. This effect was complete within 3 min and thereafter showed no further time-dependent increase. Mean passive Na influx (pmol-cm-2/s) decreased from 19.1 to 17.7 (P less than 0.05) and 10.4 (P less than 0.001) in 10(-5) and 10(-3) mol/litre procainamide, respectively. No effect on active Na extrusion was noted before 3 min following exposure to the drug, after which time it progressively declined reaching a minimum value for each concentration by 6 min and remaining at this level throughout a further 60 min exposure. For each concetnration this minimum value was similar to the Na influx measured under identical conditions. Na-coupled active K influx showed a parallel pattern of inhibition. K efflux was not decreased until approximately 20 min following exposure to the drug, but once present the reduction was similar in magnitude to that in the correspondingly measured K influx. Kinetic flux analysis revealed a decrease in both PNa and PK but indicated a greater effect on PNa. The results suggest that all of the above effects could be explained on the basis of one direct action of the drug, namely, the prompt initial decrease in PNa and Na influx. All other effects noted, both active and passive, could then be secondary to this phenomenon.

Cell Membrane Permeability↗
PubMed1976

Effect of quinidine and temperature on sodium uptake and contraction frequency of cultured rat myocardial cells.

The effects of quinidine and temperature on Na influx and contraction frequency of synchronously contracting rat myocardial cells in monolayer cultures were studied. Quinidine (10(-6) M to 10(-1) M) produced a prompt reduction in Na influx, maximum after 30 seconds of exposure, and dose-dependent along a sigmoid log dose-response curve. At 37 degrees C, Na influx (mumol/10(11) cells per sec) decreased from 30.19 to 24.70 (P less than 0.001) and 10.49 (P less than 0.001) on exposure to quinidine, 10(-6) and 10(-2) M, respectively. Simultaneously the contraction frequency decreased from a control of 120/min to 105/min and 48/min with 10(-6) M and 5 X 10(-4) M quinidine. At higher concentrations spontaneous contractions ceased. The effects on Na influx and contraction were reversible by washing the cells free of the drug (30 seconds). A temperature-dependent decrease in the Na influx between 37 degrees C and 22 degrees C also induced a decrease in contraction frequency. Between 25 degrees C and 35 degrees C the Q10 values for Na influx and contraction frequency were 2.41 and 2.44 respectively. Under all conditions tested there was a constant linear relationship (r = 0.98) between Na influx and contraction frequency for all values of Na influx greater than 11.82 mumol/10(11) cells per sec. Na influx and contraction frequency were insensitive to tetrodotoxin (10(-5) g/ml) but very sensitive to verapamil and to changes in extracellular Na. Quinidine affected only the verapamil-sensitive Na influx. The results indicate a close relationship between verapamil-sensitive inward Na movement and automaticity in these cells and demonstrate that the quinidine-induced changes in automaticity are closely linked to the effect on Na influx.

Action Potentials↗
PubMed1976

Effect of quinidine on cation exchange in cultured cells.

The effects of quinidine on membrane ion exchange were examined using monolayer cultures of mammalian cells. Quinidine, in concentrations from 10(-6) to 10(-3) M, produced a prompt inhibition of the passive Na influx, dose-dependent along a sigmoid log dose-response curve. This effect was at a maximum for each concentration of the drug within 30 seconds of application. Passive Na influx (pmol/cm2/sec) decreased from 18.8 to 17.6 (P less than .05) and 10.5 (P less than .001) in the presence of 10(-6) and 10(-3) M quinidine, respectively. In the continued presence of quinidine, there was no further time-dependent effect on the Na influx, nor was there any tendency for the influx to recover. Washing the cells free of quinidine, however, resulted in a return of Na influx to control levels within 1 to 3 minutes. After 1 to 2 minute of quinidine treatment, coupled active Na efflux/K influx rapidly declined, reaching minimum values for each concentration between 2 to 4 minutes of drug treatment. Beyond that time, active Na/K fluxes again increased, but to values which remained significantly less than control, for up to 4 hours. Ten minutes of exposure to quinidine were required before any demonstrable effect on the passive K efflux could be recorded. In the presence of quinidine, there was reduced membrane turnover of both Na and K, but such that after a brief initial period (10 minutes or less) both ions were in flux equilibrium, explaining the absence of change in [Nai] and [Ki] in the presence of quinidine. Calculations of Ec1 indicated that, when present for 4 hours, quinidine did not change the Em in these cells although significant (P less than .001) reductions in apparent PNa and Pk values were recorded. The effect on PNa was much greater than that on Pk. The quinidine-induced flux changes occurred in a definite temporal sequence suggesting that they could all be explained on the basis of one direct initial action. This initial direct action, namely the prompt reduction in Na influx, by modifying Na pump activity, could lead to a decreased K efflux, secondary to the depressed Na-coupled active K influx via the Na pump.

Biological Transport, Active↗
PubMed1972

Effect of prolonged ouabain treatment of Na, K, Cl and Ca concentration and fluxes in cultured human cells.

1. Girardi and Hela cells (derived from human heart and cervix respectively) were grown as monolayer cultures in B.M.E. (Eagles basal medium) containing concentrations of ouabain up to 5 x 10(-8)M for periods ranging up to 5 days. The cell sizes, numbers, Na, K, Cl, and Ca concentrations and fluxes were then measured.2. Twenty-four hours incubation in ouabain concentrations equal to or less than 5 x 10(-8)M caused a rise in [Na](i) and an almost equal fall in [K](i) to new steady levels. The concentrations so reached were linearly related to the ouabain concentrations, such that in 5 x 10(-8)M ouabain [Na](i) rose to 124 m-mole/l. intracellular water and [K](i) fell to 55 m-mole/l. i.c. water in Girardi cells. In Hela cells the changes were smaller at any particular ouabain concentration. These levels were maintained constant for at least 5 days.3. In cells in the logarithmic phase of growth, raising [Na](i) and lowering [K](i) by ouabain caused a slowing of growth rate proportional to the ouabain concentration used. In cells in the stationary phase there was no change in the cell numbers over 24 hr. The volume of the cells was not directly affected by the treatment.4. Reducing [K](o) from the normal value of 5.4 to 2.5 mM increased the effect of any ouabain concentration, whereas increasing [K](o) to 7.5 decreased the effect of ouabain.5. Reduction of [K](o) to 2.5 mM had no effect on the [K](i) or [Na](i) but halved the cell numbers, probably by a reduction in the growth rate. The mechanism of this effect is obscure.6. In Girardi cells raising [Na](i) and lowering [K](i) by prolonged treatment increases the total Na fluxes and decreases the total K fluxes but keeps the total Na + K flux constant. High-Na, low-K cells had a reduced Na:K exchange compared to fresh cells and also had a Na:K pumped ratio nearer 4:1 than the 3:2 normally found.7. These cells also show ouabain-sensitive and ouabain-insensitive Na:Na exchanges. In high-Na, low-K cells the ouabain sensitive Na:Na exchange is the same as in fresh cells. The effect of treatment on the ouabain insensitive Na:Na exchanges has not been elucidated.8. The Cl content and fluxes are not altered by prolonged ouabain treatment. From this it is inferred that the membrane potential in high-Na, low-K cells is the same as in normal cells.9. High-Na, low-K cells have the same calcium content and fluxes as fresh cells. From this it is concluded that there is no Na:Ca coupling in these cells.

Biological Transport↗
PubMed1972

Uptake of ( 3 H)ouabain and Na pump turnover rates in cells cultured in ouabain.

1. The binding of [(3)H]ouabain to fresh Girardi and Hela cells and to those cultured in low concentrations of ouabain for 24 hr has been measured.2. Fresh cells bind 1.6-2.2 x 10(6) molecules of ouabain(*) per cell from K-free Krebs, but less than 0.3 x 10(6) molecules from 15 mM-[K](o) Krebs. The ouabain(*) binds with a t((1/2)) of about 8 min from K-free 2 x 10(-7)M ouabain(*) and is released with a t((1/2)) of about 20 hr. Cells in a poor condition probably exchange ouabain more quickly.3. Cells incubated in ouabain(*) for 24 hr bind ouabain in amounts dependent on the [ouabain] and the external [K]. At the highest [ouabain] used the total amount bound exceeds that bound by fresh cells. Lowering [K](o) in the medium increases the maximum ouabain which is bound.4. Cells incubated in ouabain(*) for 24 hr bind an additional amount of ouabain when exposed to 2 x 10(-7)M ouabain(*) in K-free Krebs.5. There is a close relationship between the% of the total ouabain bound in 24 hr and the% inhibition of the Na efflux suggesting that this ouabain is bound to the Na pumps.6. Radiochromatography of the counts recovered from the cells showed that it migrated to the same place as the applied [(3)H]ouabain. The wash-off rate of ouabain bound to cells during incubation is similar to that from fresh cells, both tests suggesting that the ouabain exists in the same state in the cells.7. The number of Na ions extruded per pump is constant at about 60 sec(-1) in fresh cells and those pre-incubated in ouabain.8. The total ouabain bound by the cells is closely related to the [Na](i) in cells pre-incubated in ouabain but is unaffected by it in fresh cells where [Na](i) is raised acutely.9. These results are compatible with the hypothesis that partial blocking of Na pumps leads to the production of more pumping sites by the cell.

Binding Sites↗
PubMedDate not supplied

Eosinophilic heart disease presenting with features suggesting hypertrophic obstructive cardiomyopathy.

We report a 25-year-old female with characteristic features of eosinophilic heart disease on clinical presentation, echocardiography, cardiac catheterization, and LV endomyocardial biopsy. Concomitant physical examination and echocardiographic findings suggesting hypertrophic obstructive cardiomyopathy resolved during treatment with anticoagulation and prednisone therapy.

Adult↗
PubMedDate not supplied

Effect of ischemia-related metabolic factors on thallium exchange in cultured rat myocardial cells.

Failure of the myocardium to take up Thallium-201 is widely used as a diagnostic marker for ischemia or infarction. Although this is commonly related to a reduction in coronary flow or myocardial perfusion, other possible metabolic factors are poorly understood. The present studies investigated the influence of various interventions, designed to simulate the metabolic consequences of ischemia, on thallium-204 uptake and release in cultured myocardial cells. In these cells, where thallium exchanged rapidly (t 1/2 = 5 min.), and 60% of thallium uptake occurred via the sodium pump, thallium uptake was markedly influence by changes in extracellular potassium. Increasing extracellular potassium from a physiologic level of 5 mM to those levels reported to occur in ischemic myocardium (7.5 mM to 18 mM) effected a 25% to 60% reduction in thallium influx. The decrease in thallium influx produced by increasing extracellular potassium was rapid (30 sec.) in onset and readily reversible by restoring extracellular potassium towards normal. Changes in extracellular pH in the range 6.4 to 8.0 had no demonstrable effect on thallium uptake despite the fact that this was accompanied by similar, although less marked, changes in intracellular pH. Addition of adenine nucleosides, adenosine, inosine and hypoxanthine, to the incubating solution in concentrations from 1 nM to 0.1 mM had no effect on thallium influx or efflux in the cells. This observation held true even when 10 microM dipyridamole was used to inhibit nucleoside uptake by the cells. Addition of 1 mM 2, 4-dinitrophenol or 4 mM potassium cyanide to the cultures maximally inhibited 42% of the thallium influx within 30 min.(ABSTRACT TRUNCATED AT 250 WORDS)

2,4-Dinitrophenol↗