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D Ellis

Publications and source records attributed to D Ellis.

At least 37 records · Page 2Linked to original sources

Changes in the intracellular sodium activity of sheep heart Purkinje fibres produced by calcium and other divalent cations.

1. The intracellular Na activity of sheep heart Purkinje fibres was recorded with Na+-sensitive glass micro-electrodes. The effects of various external divalent cations on the intracellular Na activity were investigated. 2. Raising the external concentration of divalent cations (Ca, Mg, Mn, Sr or Ba) from 3 to 16 mM resulted in a decrease in the intracellular Na activity of 10-50%. 3. Raising the external concentration of Ca, Sr or Ba could produce a decrease in the intracellular Na activity even when the Na-K pump was inhibited (with strophanthidin, 10(-5) M); but raising the external concentration of Mg or Mn could not. 4. Mn inhibited the decrease in the intracellular Na activity produced by raising external Ca while the Na-K pump was inhibited. 5. Raising external Ca or adding Mn reduced the rate of rise of the intracellular Na activity on inhibition of the Na-K pump. 6. The removal of external K resulted in an increase in the intracellular Na activity. This increase could be stopped and even reversed by raising external Ca. 7. Removal of divalent cations from the external solution produced an increase in the intracellular Na activity. However, replacing external Ca and Mg by another divalent cation, e.g. Mn, did not result in a rise in the intracellular Na activity, except when the Na-K pump was inhibited. 8. The intracellular Na activity decreased by approximately 50% for a tenfold increase in the external Ca concentration. 9. The extent of the decrease in internal Na activity produced by raising external Ca was directly proportional to the internal Na activity before external Ca was raised. 10. We conclude that external Ca influences the intracellular Na activity in two ways: (a) by changing the passive Na influx: the resultant change in the intracellular Na depends on the activity of the Na-K pump; and (b) by a process where internal Na ions are exchanged for external Ca ions.

Animals

The intracellular sodium activity of cardiac Purkinje fibres during inhibition and re-activation of the Na-K pump.

1. The intracellular Na activity, aiNa, of sheep heart Purkinje fibres was continuously monitored using Na+-sensitive glass micro-electrodes. The effects of removal and restoration of external K, and of application and removal of various cardioactive steroids, were investigated. 2. The aiNa increased in K-free solutions and rapidly recovered on addition of external K. The rate of this recovery depended on both the external K concentration, [K]o, and the aiNa. The rate of aiNa recovery was found to be half maximally activated at a [K]o of about 10 mM. If corrections are applied to allow for changes in the net passive Na influx at various [K]o, then this value is increased to approximately 12.5 mM. 3. At a given [K]o, there appeared to be a linear relationship between the rate of aiNa recovery and the level to which aiNa had increased in K-free solution (over the range of aiNa from 7.5 to 31 mM). 4. Addition of the cardioactive steroids strophanthidin, acetylstrophanthidin, actodigin (AY 22,241) or dihydro-ouabain produced rapid changes of aiNa. At low concentrations, these compounds sometimes produced a small decrease in aiNa, while at concentrations above 10(-7) M they produced a dose-dependent increase. 5. The effects on aiNa of both low and high concentrations of all these cardioactive steroids were readily reversible within 120 min. The time course of the aiNa recovery mainly depended on the concentration of the cardioactive steroid applied, and on the level to which aiNa had increased. 6. Upon addition of a cardioactive steroid (above 10(-7) M, aiNa at first increased almost linearly with time. The rates of such an increase were measured during this period at various cardioactive steroid concentrations and used to produce dose-response curves. The concentrations that produced a half-maximum rate of aiNa increase were near to 10(-6) M for strophanthidin and acetylstrophanthidin, but near to 10(-5) M for actodigin and dihydro-ouabain. 7. The mean maximum rate of aiNa increase produced by the addition of a high cardioactive steroid concentration was 0.49 +/- 0.17 mM/min (+/-S.D., n = 21). This would indicate a net passive Na influx into the cells of approximately 2.8 p-mole/cm2sec. 8. This maximum rate of aiNa increase could be achieved by the addition of 10(-5) M-strophanthidin or acetylstrophanthidin, but 10(-4) to 10(-3) M-actodigin or dihydro-ouabain was required to produce a similar rate of increase. 9. The addition of these high cardioactive steroid concentrations produced an initially rapid increase of aiNa. After 15-30 min this aiNa increase slowed considerably. The aiNa appeared to reach a 'plateau' within 2-4 hr at levels much below those predicted for a Na electrochemical equilibrium across the cell membrane.

Animals

The effects of manganese ions on the contraction of the frog's heart.

1. The effects of Mn(2+) in particular but also of Ni(2+), Co(2+), Cd(2+), verapamil and D600 on the contraction of isolated frog atrial trabeculae have been investigated. Contraction was initiated either by electrical stimulation, or by raising the [K](o) or by lowering the [Na](o).2. Mn ions like Ca ions cause a hyperpolarization of the cell membrane and a rise in the threshold for the action potential and twitch. Mn ions, particularly at low concentrations, reduce the overshoot of the ventricular action potential.3. Mn ions reduce the strength of the regularly evoked heart beats. Prolonged exposure, in beating hearts, results in a rise in resting tension and often a small recovery of the heart beat.4. In normal Ringer solution and in Ringer free of Na ions, the addition of Mn causes the tension-depolarization curve to be displaced by an amount equivalent to an 18 mV hyperpolarization of the membrane potential for a tenfold increase in the divalent cation concentration.5. Mn, Co, Ni and Cd ions all cause a marked reduction in the tension generated by exclusion of Na ions from the bathing fluid. In the presence of these divalent cations the contracture divides into an initial phasic and a later tonic contraction. This inhibition is reversed by raising the [Ca](o), while the tension developed during the initial phasic contraction varies with the [Ca](o)/[Mn](o) quotient.6. A similar tonic contracture is initiated after exposure to Na-free fluid containing a high [Mn](o) by the addition of a small concentration of Na, Li, hydrazinium or hydroxylammonium ions.7. The organic ;Ca antagonists' verapamil and D600 have little effect on the contracture induced by lowering [Na](o) even after prolonged exposure at relatively high concentrations but they do inhibit the twitch contraction and the K contractures.8. The effects of Mn on the Na-withdrawal contracture of frog heart can be interpreted in terms of an exclusively extracellular effect where Mn ions resemble Na ions in their action, and both antagonize the movement of Ca across the cell membrane.9. The experimental evidence suggests that the K contracture in frog heart is initiated by a mechanism which is, in some ways different to that underlying the Na-withdrawal contracture, and may involve two different sources of activator Ca.10. The several different effects of Mn on the frog heart probably reflects the ability of this cation to interfere with many processes involving Ca, and that there are a number of such processes involved in the results described in this work. The effects of Mn are more complex than might be generally supposed.

Animals

Uptake and loss of manganese from perfused frog ventricles.

1. The uptake and loss of Mn has been studied in perfused isolated frog ventricles, at rest, during activity, in Na-free fluid and in K-rich fluid. 2. In normal Ringer the uptake of Mn with time is composed of two phases which can be interpreted as an initial saturating phase and a slower non-saturating phase. The uptake in the resting heart is estimated to be 1.91 X 10(-14) M.cm-2.sec-1, and the extra uptake associated with the action potential to be 6.90 X 10(-13) M.cm-2.beat-1, when the heart is exposed to Ringer containing 8 mM-Mn. 3. The washout of Mn from preloaded ventricles into Mn-free Ringer is composed of at least two exponential phases. The slowest phase corresponding to a rate of Mn efflux of 1.72 X 10(-14) M.cm-2.sec-1. 4. Mn uptake is not increased by exposure of the muscle to Na-free fluids but is markedly increased by exposure to depolarizing fluids. 5. The Mn accumulating in the ventricles during a 7 1/2 min exposure to 8 mM-Mn-ringer with an elevated [K], increases with increasing [K]o to reach a peak at 75 mM-K and then falls to quite a low value in 120 mM-K. 6. The results are discussed in the light of the action of Mn ions on the contraction and the ionic currents of frog heart muscle.

Animals

The effects of external cations and ouabain on the intracellular sodium activity of sheep heart Purkinje fibres.

1. The intracellular Na activity of sheep heart Purkinje fibres has been measured using recessed-tip Na(+)-sensitive glass micro-electrodes.2. The internal Na activity was 7.2 +/- 2.0 mM (mean +/- S.D., n = 32) at the normal external Na concentration, [Na](o), in these experiments of 140 mM (equivalent to an external Na activity of 105 mM). The equilibrium potential for Na across the fibre membrane was therefore approximately + 70 mV.3. When the [K](o) was altered the internal Na activity changed, reaching a new level within about 20 min. Increasing the [K](o) from 4 to 25 mM decreased the internal Na by approximately 30%, while decreasing the [K](o) from 4 to 1 mM increased internal Na by 20%.4. The removal of external K produced an easily reversible increase in the internal Na with an initial rate equivalent to a concentration change of 0.24 +/- 0.07 m-mole/min (mean +/- S.D., n = 8).5. Ouabain produced increases in the internal Na activity that were only very slowly reversible. The threshold concentration for producing an increase was approximately 10(-7)M.6. When [Na](o) was reduced the internal Na activity fell rapidly with a single exponential time course (time constant 3.3 +/- 0.8 min, mean +/- S.D., n = 16) to a new, relatively stable level. The recovery of internal Na on return to the normal [Na](o) did not have a simple time course. It was normally complete within 10-30 min.7. The relationship of the stabilized level of the internal Na activity to the [Na](o) was approximately linear over the range 140-14 mM-[Na](o). When [Na](o) was reduced from 140 to 14 mM the internal Na activity fell by 72 +/- 5% (mean +/- S.D., n = 21).8. When the [Na](o) was reduced, the decrease in the internal Na activity was partially inhibited by Mn or by removal external Ca.9. When the [Ca](o) was altered over the range 0.2-16 mM the internal Na activity was reduced by approximately 50% for a tenfold increase in the [Ca](o).10. The relationship between internal Na and contractility is discussed.

Animals

New approach to evaluation of proteinuric states.

We evaluated the use of immunonephelometric methods for measuring specific urinary proteins. Using a nephelometer to detect light scattering (angle, 31 degrees), we measured some proteins immunonephelometrically in serum and aliquots of 24-h urines from 50 apparently healthy children, ages 2-17 years. The mean urinary excretion rate (mg/24h) and the range of values was: for albumin 5.5 (range, 0-13.3), for transferrin 0.5 (0-1.9, for IgG 3.3 0-12), and for alpha 2-macroglobulin 0.6 (0-2.3). Direct comparison of the values for pathological urines with those for a reference population may offer more meaningful information concerning the integrity of the glomerular basement membrane than is provided by protein selectivity indices, and measuring a plasma protein such as albumin in urine may better define pathological proteinuria.

Adolescent

Direct measurement of the intracellular pH of mammalian cardiac muscle.

1. The intracellular pH (pHi) of sheep heart Purkinje fibres and rat, ferret and guinea-pig ventricle has been measured using recessed-tip pH-sensitive micro-electrodes. 2. In the absence of CO2 the pHi was approximately 7-2 in all the preparations used. In 5% CO2 the mean pHi was 7-14 in rat and ferret ventricle and 7-02 in sheep Purkinje fibres. 3. The pHi response to an increase or a decrease in the CO2 level (at constant external pH) was biphasic with a large transient change followed by a partial recovery to a new sustained pHi. 4. The intracellular buffering capacity was 34-8 +/- 2-7 m-equiv H+/pH unit per l. (+/- S.E. of mean) in sheep Purkinje fibres, 76-6 +/- 13-6 in rat ventricle and approximately 69 in ferret ventricle. 5. The pHi of all the preparations tested indicated that H+ ions were not passively distributed across the cell membrane. There was also little or no pHi change produced by depolarization with high K solutions. 6. Short exposures to hypertonic solutions (100 mM sucrose or 50 mM-KCl) produced a decrease in pHi of approximately 0-1 pH units. 7. Acetazolamide slowed the pHi response to CO2 changes. 8. Restoration of the pHi after displacement by increasing the CO2 was not blocked by ouabain or SITS. 9. The relationship between pHi and cardiac contractility is discussed.

Acetazolamide