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Biomedical subjects

J M Ritchie

Publications and source records attributed to J M Ritchie.

At least 127 records · Page 7Linked to original sources
PubMed1970

The binding of tritiated ouabain to mammalian non-myelinated nerve fibres.

1. A study has been made of the binding of radioactively labelled ouabain by desheathed rabbit vagus nerves, which consist mainly of non-myelinated fibres. The corresponding inhibition of the electrogenic sodium pump was also measured.2. By varying the ouabain concentration and the external potassium concentration two kinds of binding sites could be distinguished: a first site specifically associated with pumping and whose ability to bind ouabain is dependent on the external presence of potassium; and a second site not associated with pumping and unaffected by external potassium.3. Just complete inhibition of the sodium pumping mechanism is associated with a specific binding of ouabain of about 4.3 p-mole/mg dry nerve.4. This gives an upper limit for the density of sodium pumping sites of about 750 per square micron.5. The turnover rate (i.e. (cation pumped)/(number of sites)) at 20 degrees C is about 22 sec(-1).

Animals↗
PubMed1969

On the metabolic basis of nervous activity.

1. A study has been made of the metabolic substrates that can support the active extrusion of sodium ions from mammalian non-myelinated nerve fibres. The post-tetanic hyperpolarization obtained in chloride-free Locke solution, which reflects the electrogenic component of the sodium pump, was used as the index of metabolic activity.2. When glucose was removed from the Locke solution there was no immediate change in the size of the post-tetanic hyperpolarization.3. However, glucose is essential for metabolism in nerve fibres; for when a competitive inhibitor, deoxy-D-glucose, was added to the Locke solution the post-tetanic response was much reduced or abolished. Larger concentrations of deoxy-D-glucose were required in the presence of glucose than in its absence.4. This effect of deoxy-D-glucose could be reversed by glucose, fructose, pyruvate and acetate.5. The depressant effect of deoxy-D-glucose was enhanced by oxaloacetate and by malate.6. Malonate, a competitive inhibitor of the conversion of succinate to fumarate, reduced or abolished the post-tetanic hyperpolarization.7. This effect of malonate could be overcome by glucose and by pyruvate.

Acetates↗
PubMed1969

A comparison of the effect of temperature, metabolic inhibitors and of ouabain on the electrogenic componen of the sodium pump in mammalian non-myelinated nerve fibres.

1. A comparison has been made of the effect of cooling, metabolic inhibitors and of ouabain on the electrogenic component of the sodium pump in mammalian non-myelinated nerve fibres.2. The hyperpolarization that occurs during the potassium-activated response that is obtained after a brief period of stimulation (5 sec, 30/sec) in potassium-free solution was taken as an index of the activity of the pump.3. Cooling decreased the amplitude and rate constant of decay of the potassium-activated response. The area of the response, which reflects the total amount of sodium that is extruded after activity, remained constant.4. Exposure to the metabolic inhibitors deoxy-D-glucose and cyanide also decreased the amplitude and rate constant of the response; as with cooling, the area remained relatively constant.5. Ouabain, however, reduced the amplitude without reducing the rate constant, which was even sometimes increased with small concentrations of ouabain. The area of the response always decreased therefore.6. The effects applying metabolic inhibitors are thus similar to those obtained on cooling, but differ from those of ouabain.

Animals↗
PubMed1968

Local anesthetics: effect of pH on activity.

Lidocaine and dibucaine are more effective in neutral than in alkaline solution when tested on the nonmyelinated fibers of the desheathed vagus nerve of the rabbit. Procaine, however, is more effective in alkaline solution. The activity of benzocaine is unaffected by pH. Both the charged and uncharged forms of local anesthetics thus seem capable of blocking conduction.

Action Potentials↗
PubMed1968

The origin of the initial heat associated with a single impulse in mammalian non-myelinated nerve fibres.

1. A study has been made of the temperature changes associated with the passage of a single impulse in rabbit desheated vagus nerves.2. The initial changes consist of an evolution of positive heat followed by a reabsorption of most of it; i.e. there is a phase of positive and a phase of negative heat production.3. The size of the positive heat, its time of onset, and the time of onset of the negative heat have been measured by an analogue method of analysis. In addition, these parameters, together with the size of the negative heat and the duration of both phases of initial heat, have been studied with the aid of a computer, and also by conventional heat block analysis.4. At about 5 degrees C the measured positive heat is 7.2 mucal/g. impulse. It starts as soon as the compound action potential reaches the thermopile and lasts for about 107 msec.5. This positive heat decreases with increasing temperature, the ratio of heat at 4 degrees C to that at 14 degrees C being 1.86.6. The measured negative heat at about 5 degrees C is 4.9 mucal/g. impulse. It starts 102 msec after the onset of positive heat, and lasts for about 240 msec.7. When the sodium of Locke solution is replaced by lithium the positive heat is reduced by 19%, but the negative heat is increased by 22%.8. In potassium-free solutions the positive heat is hardly affected (increase of 5%), but the negative heat is more than doubled. As a result the nerve may become briefly colder than its initial temperature by about 2 mu degrees C.9. The effect of sodium-deficient solutions on the positive heat is somewhat variable, but the negative heat is consistently diminished.10. Replacement of the chloride of Locke solution by sulphate or nitrate has little effect on the positive heat. The negative heat is reduced in size by 26% and in duration by 22%.11. Replacement of most of the sodium of Locke solution by barium reduces or abolishes the negative heat, and increases the measured size of the positive heat nearly threefold.12. Veratrine (10(-5) g/ml.) produces a nearly tenfold increase in the net positive heat.13. Ouabain (1 mM) and antimycin A (1 mug/ml.) applied for 30-60 min have little effect on the initial heat production.14. Over the temperature range 5-15 degrees C, and for the ionic solution changes described above, there is close agreement in timing between the positive heat and the rising phase of the action potential, and between the negative heat and the falling phase.15. Because of the inevitable temporal dispersion of the action potential over the face of the thermopile, the observed temperature changes are smaller than those which occur at a single point in the nerve close to a stimulating electrode. The corrected value of the positive heat at 5 degrees C is 24.5 mucal/g. impulse, while that of the negative heat is 22.2 mucal/g. impulse.16. The heats of mixing of the ions in solution that interchange during the action potential are much too small to account for the observed initial heats, but an exchange of ions associated with fixed charges might make a significant contribution to the heats.17. The condenser theory, according to which the positive heat represents the dissipation of electrical energy stored in the membrane capacity, while the negative heat results from the recharging of the capacity, appears unable to account for more than half of the observed temperature changes.18. It seems probable that the greater part of the initial heat results from changes in the entropy of the nerve membrane when it is depolarized and repolarized.

Action Potentials↗
PubMed1968

The dependence on external cations of the oxygen consumption of mammalian non-myelinated fibres at rest and during activity.

1. A study has been made of the effect of potassium and other cations on the oxygen consumption of rabbit desheathed vagus nerves at rest and during activity.2. In normal Locke solution (containing 5.6 mM-K) the resting oxygen consumption, Q(r), was 0.0903 mumole/g wet wt. min. The extra oxygen consumed as a result of stimulation, Q(s), at 3 stimuli/sec was about 600 p-mole/g.impulse; at 30 stimuli/sec it was less, being 240 p-mole/g.impulse.3. Only a fraction of Q(r) (18% at 5.6 mM-K) was sensitive to ouabain (1 mM). The ouabain-sensitive component, however, increased as the external potassium concentration was increased, in the range 0-100 mM. Q(s) was virtually abolished by ouabain.4. Reduction of the external potassium concentration from 5.6 mM to zero reduced Q(r) (by 10%) and increased Q(s), but the changes were scarcely significant statistically.5. The conclusions were drawn: that Q(s) reflected the pumping of cations to restore the ionic imbalance following activity, particularly reflecting the extrusion of sodium ions from the fibre; that this pumping was normally absolutely dependent on the presence of potassium externally and that no pumping could occur in its absence; and that Q(s) was not reduced to zero in ostensibly potassium-free solutions because enough potassium was released into the periaxonal space during activity to maintain pumping.6. Thallium, rubidium, caesium and lithium could replace potassium and allowed pumping to occur.

Animals↗
PubMed1968

On the electrogenic sodium pump in mammalian non-myelinated nerve fibres and its activation by various external cations.

1. A study has been made of the hyperpolarization that follows a period of electrical activity (the post-tetanic hyperpolarization) in mammalian non-myelinated nerve fibres.2. Evidence is presented that under certain circumstances this postetanic hyperpolarization is a result of activity of an electrogenic sodium pump that normally is absolutely dependent on the external presence of potassium.3. When the external chloride is replaced by sulphate or by isethionate the post-tetanic hyperpolarization, which in normal Locke solution is only a few millivolts in amplitude, is increased usually to about 20 mV, and on occasion to 35 mV.4. This effect of removing the chloride takes several minutes to develop and is consistent with the idea that the increase in the post-tetanic response is the result of removing the short-circuiting effect of internal chloride ions (by their being washed out into the chloride-free bathing medium).5. Small anions, such as chloride, nitrate, iodide, bromide, and thiocyanate can short-circuit the electrogenic pump, whereas larger anions such as sulphate and isethionate cannot. The bicarbonate ion, which is larger than chloride, short-circuits the pump but less effectively.6. In Locke solution containing 5 mM potassium the post-tetanic hyperpolarization declines exponentially, with a time constant of about 1-3 min. The time constant is inversely related to the external potassium concentration.7. However, when the external potassium concentration is zero the hyperpolarization declines rapidly to a very small value. Subsequent addition of potassium to the bathing medium causes a marked redevelopment of the hyperpolarization.8. This potassium-activated response declines exponentially with a time constant that is inversely related to the potassium concentration. When the added potassium concentration is 5 mM, the time constant is 1.9 min.9. The amplitude of the potassium-activated response increases with increasing concentrations of potassium.10. Other cations can produce this activated response. Thus, thallium is more effective than, rubidium as effective as, caesium and ammonium about 1/10 as effective as, and lithium ions about 1/30 as effective as potassium in producing the activated response. Choline is quite ineffective.11. The size of the post-tetanic response is little affected by changes in the duration of the period of stimulation. However, increasing the duration definitely increases the time constant of recovery.12. Reducing the external sodium concentration increases the size of the post-tetanic hyperpolarization (by about 25%), but the effect is complex and requires further study.13. Reducing the calcium of the Locke-solution from 2.2 to 0.2 mM has no appreciable effect on the post-tetanic response, nor has increasing the pH of the Locke from 7.2 to 9.2.14. When the membrane potential is increased or decreased, by externally applied currents, there is relatively little change in the post-tetanic response.15. A mathematical model of the electrogenic pump, devised to mimic the experimental results, was analysed with an analogue computer. A satisfactory agreement between model and experiment was achieved by a model in which: (1) the rate of extrusion of sodium ions depends on the degree to which a pool of carrier molecules on the inside surface of the membrane is combined with sodium; (2) each carrier molecule transfers three sodium ions at a time; (3) the rate constant for extrusion of sodium ions also depends on the presence externally of potassium ions, which combine with some sites on the external surface of the membrane that are half-saturated when the external concentration of potassium is 2.8 mM.

Action Potentials↗
PubMed1968

The ionic content of mammalian non-myelinated nerve fibres and its alteration as a result of electrical activity.

1. A study has been made of the ionic content, and of the fibre water, of rabbit desheathed vagus nerves at rest and after activity in various modified Locke solutions.2. In normal Locke solution the intracellular sodium amounted to 86.1 mumole/g dry, and the intracellular potassium 186.0 mumole/g dry. Since the fibre water amounted to 1.124 g/g dry the intracellular sodium and potassium concentrations were 76.6 and 165.5 m-mole/kg fibre water, respectively.3. In potassium-free Locke solution the intracellular sodium and potassium concentrations were 111.0 and 121.7 m-mole/kg, respectively. The intracellular chloride concentration was 40.5 m-mole/kg.4. In normal Locke solution, a brief period of stimulation followed by a 10 min recovery period produced no significant change in the intracellular contents of potassium, sodium, or water.5. However, in chloride-Locke solution from which the potassium had been omitted, or to which ouabain (1 mM) had been added, stimulation caused a loss of potassium per impulse of about 20 p-mole/mg dry, i.e. about 4 p-mole/mg wet. A similar loss was found in isethionate-Locke solution that was potassium-free. There was no significant change in any of the other quantities measured (sodium, chloride, and fibre water).6. The efflux of radioactively labelled potassium was measured in potassium-free Locke solution at rest (k(r)) and during activity (k(s)). At 24 degrees C, k(r) was 0.0084 min(-1) and k(s) was 0.000178 impulse(-1).7. When the chloride of Locke solution was replaced by isethionate there was an increase in both k(r) (about 12%) and k(s) (about 21%).8. Ouabain (1 mM) increased k(s) (by about 70%). This increase seemed to be independent of whether the anion present was chloride or isethionate.9. It is argued that these results indicate that the electrogenicity of the pump plays a relatively small role in maintaining the ionic balance in mammalina C fibres.

Amidines↗
PubMed1967

The oxygen consumption of mammalian non-myelinated nerve fibres at rest and during activity.

1. A study has been made of the oxygen consumption of non-myelinated nerve fibres of rabbit desheathed cervical vagus nerves at rest and during activity.2. The average resting oxygen consumption (Q(r)) was 0.0924 mumole/g. min at 21 degrees C. Stimulation for 1-3 min at 3/sec caused an extra oxygen consumption (Q(s)) of 816 p-mole/g.shock.3. When the frequency of stimulation was increased, to 10/sec and 30/sec, Q(s) fell. When the frequency was decreased, to 1/sec and 0.3/sec, Q(s) increased slightly.4. When the temperature was decreased, Q(r) fell; when the temperature was increased, Q(s) also increased. Temperature similarly affected Q(s) with high frequencies of stimulation, but had relatively little effect on Q(s) at low frequencies of stimulation.5. An isolated single shock seemed to produce an increase in oxygen consumption of about 1200 p-mole/g, and this value was largely independent of temperature.6. When part of the sodium in the Locke solution was replaced by barium, Q(r) decreased (by 12%) whereas Q(s) increased (by 87%).7. Veratrine (1 mug/ml.) increased both Q(r) (by 142%) and Q(s) (by 361%).8. Acetylcholine (1.7 mM) increased Q(r) (by 32%).9. When nerves were transferred to potassium-free solutions there was little change in Q(r), and Q(s) fell slightly (by 8%).10. When the potassium concentration in the Locke solution was increased 4-fold, Q(r) increased (by 27%).11. Salicylate (1-10 mM) increased Q(r) (by 24%) and abolished Q(s).12. When the sodium of Locke solution was replaced by lithium, Q(r) decreased (by 19%) and Q(s) was abolished.13. In sodium-Locke solution ouabain (100 muM) decreased Q(r) (by 26%) and abolished Q(s). In lithium-Locke solution ouabain also decreased Q(r) (by 28%).14. All or nearly all of the oxygen consumed at rest or during activity seemed to be used to pump potassium ions into, and sodium ions out of, the axoplasm.15. The K/O(2) ratio during pumping was about 5.0.

Acetylcholine↗