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J M Ritchie

Publications and source records attributed to J M Ritchie.

At least 73 records · Page 4Linked to original sources
PubMed1982

On the relation between fibre diameter and conduction velocity in myelinated nerve fibres.

Myelinated fibres less than 1 micrometer in diameter are rare in the peripheral nervous system; but fibres down to 0.2 micrometer in diameter exist in the central nervous system. These observations are consistent with Rushton's theory on the effects of fibre size on conduction in myelinated nerve when the different processes of myelination in the peripheral and central nervous systems are taken into account.

Action Potentials↗
PubMed1982

Sodium and potassium channels in regenerating and developing mammalian myelinated nerves.

A study has been made of how the normal complementary distribution of sodium and potassium channels in mammalian myelinated nerve fibres (all the sodium channels being in the node with all the potassium channels in the internode) is altered in regenerating and in developing rabbit sciatic nerves. In regenerating nerve fibres, where a marked increase in the number of nodes per unit length occurs, there is a corresponding increase in the sodium channel content (determined from the maximum saturable binding of labelled saxitoxin), consistent with the idea that the number of sodium channels per node remains roughly constant. The use of 4-aminopyridine, which by blocking potassium channels prolongs the action potential, has shown that both in regenerating nerve fibres and in developing nerve fibres potassium currents contribute to the mammalian action potential. In both cases, with the passage of time, the sensitivity to 4-aminopyridine progressively decreases.

Action Potentials↗
PubMed1982

Evidence for the presence of potassium channels in the internode of frog myelinated nerve fibres.

1. The central portion of single frog internodes under voltage-clamp conditions was acutely demyelinated with lysolecithin to resolve whether potassium channels are normally present only in the paranode (Chiu & Ritchie, 1980, 1981) or are in fact present throughout the entire internode of a myelinated nerve fibre. 2. The experiments were performed in the absence of nodes of Ranvier to ensure that all currents observed originated from the internode. 3. The demyelinating internodal segment showed a steady increase in the capacity and leakage for the first 40--50 min, after which a delayed outward current was revealed. This delayed current, which was blocked by TEA and caesium and exhibited a potassium-dependent reversal potential, seems to be a potassium current similar to that normally present in the frog node and in squid nerve. 4. The present method of acute demyelination revealed no detectable sodium currents in the internodal segments. 5. These results suggest that potassium channels, but virtually no sodium channels, are normally present throughout a frog internode covered by the myelin.

Animals↗
PubMed1981

Evidence for the presence of potassium channels in the paranodal region of acutely demyelinated mammalian single nerve fibres.

1. A study has been made of the ionic currents in voltage-clamped single rabbit nodes of Ranvier at 22-26 degrees C both under normal conditions, and after the nerve fibres had been acutely demyelinated by a variety of treatments designed to lossen the myelin from the axonal membrane. 2. The myelin-loosening treatments included application of various combinations of: lysolecithin (to dissolve the myelin); collagenase (to loosen the connective tissue in the nodal region); high-potassium Locke solution, hypertonic and hypotonic solutions (to induce axonal volume changes). 3. At a critical stage in such treatment (usually after 15-45 min) a large outward current suddenly appeared. 4. There was no substantial change in the size of the measured inward sodium current when measured at this critical stage. 5. The outward current was blocked by internal TEA and caesium ions, had a reversal potential that became more positive when the external potassium concentration was increased, was kinetically similar to the known potassium current in frog fibres, and was therefore assumed to be a potassium current. 6. The phase of large outward current, whenever it appeared, was always accompanied by the appearance of a slow transient capacitative component in the leakage current, which indicated a marked increase in the effective nodal capacity (of 10- to 60-fold). We suggest that the slow transient capacity current reflected charging of newly exposed axonal membrane, probably in the paranodal region, which was uncovered by the various acute demyelination treatments. This internodal membrane seems to contain mostly potassium channels and few, if any, sodium channels. 7. Newly dissected fibres occasionally showed large potassium currents before treatment, particularly if they were deliberately stretched during dissection; a marked slow capacity transient current was consistently present in these fibres. 8. The effects of acute paranodal demyelination on the sodium and potassium currents, and on the transient capacity currents, can be simulated by a model in which the node is coupled to a cable-like paranode which contains Hodgkin--Huxley type potassium channels and which has a much higher leakage resistance. 9. The functional significance of the presence of potassium channels in rhe internodal region (at least in the paranode) of mammalian fibres is discussed.

Animals↗
PubMed1980

Potassium channels in nodal and internodal axonal membrane of mammalian myelinated fibres.

Horakova et al. were the first to observe that the phase of late outward current carried by potassium ions in frog and squid nerve is virtually absent in voltage-clamped rat nodes of Ranvier. This observation has been recently confirmed by Chiu et al. in rabbit nodes of Ranvier, suggesting that the nodal membrane in the mammal generally has few if any potassium channels. The present voltage-clamp experiments show that large potassium currents can, however, be produced in normal rabbit nodes of Ranvier by acute treatment designed to loosen the myelin from the axonal membrane. From this we conclude that whereas potassium channels are absent in the mammalian nodal membrane, they are normally present in the internodal axonal membrane at least in the paranodal region.

Animals↗
PubMed1980

Oxygen consumption and phosphate efflux in mammalian non-myelinated nerve fibres.

1. A comparison has been made between the efflux of labelled phosphate from the non-myelinated fibres of the desheathed rabbit vagus nerve at 37 degrees C and the corresponding O2 consumption at rest and during activity, and during a variety of experimental interventions. 2. The resting rate constant of phosphate efflux was 2.61 X 10(-3) min-1: electrical stimulation (10 sec-1, 3 min) produced an extra fractional loss of 6.75 X 10(-6) impulse-1. 3. The corresponding resting O2 consumption was 0.484 m-mole x kg-1 impulse-1. 4. Ouabain (100 microM) produced a sustained depression (of about 40%) of the resting O2 consumption, accompanied by a transient fall (of about 14%) in the rate constant of phosphate efflux. 5. Na salicylate (10 mM) or Na arsenate (1 mM) produced a much larger increase in phosphate efflux than in resting O2 consumption. 6. Changing the external phosphate concentration (between 0.02 and 2 mM), addition of acetylcholine (1.7 mM), and addition of lanthanum (20 microM)--all of which are known to affect markedly the phosphate efflux in rabbit non-myelinated fibres--had little or no effect on the resting O2 consumption or, where tested, on the extra O2 consumption with electrical stimulation. 7. Changing the external Ca concentration (between 0.09 and 9 mM) had only minor effects on the O2 consumption (resting and stimulated) and on the rate constant of resting phosphate efflux. 8. It is concluded that although changes in metabolism of the nerve produce changes in the phosphate efflux expected on the basis of the concomitant changes in the internal concentration of inorganic phosphate, the converse is not true; and increases and decreases in the rate constant of phosphate efflux do not necessarily signal the corresponding metabolic changes.

Animals↗
PubMed1980

Observations on the mechanism for the active extrusion of lithium in mammalian non-myelinated nerve fibres.

1. A study has been made of the O2 consumption, and the corresponding efflux of labelled phosphate, from the non-myelinated fibres of the desheathed rabbit vagus nerve at 37 degrees C in Locke solutions in which various ions were substituted for Na, and also in the presence of ouabain. 2. Switching from Na-Locke solution to Li-Locke solution produced a small transient decrease in the resting O2 consumption (of 14%), which rapidly recovered to its original value. This was accompanied by an initial brief rise followed by a maintained fall in the resting phosphate efflux. 3. In Li-Locke solution, ouabain (100 microM) produced a fall in the resting O2 consumption of 40%, i.e. similar to that produced in Na-Locke solution. Any depression of the resting phosphate efflux was absent or small. 4. In choline-Locke solution, in Tris-Locke solution, in K-Locke solution or in sucrose-Locke solution the resting O2 consumption, which fell by 30-40%, was insensitive to the addition of ouabain (100 microM). 5. Addition of either Na ions or of Li ions partially restored respiration in choline-Locke solution, Li being an order of magnitude less effective than Na. 6. In choline-Locke solution the internal K content was not affected by ouabain. However, if Li (77 mM) was present in the bathing solution ouabain (100 microM) produced a 30% fall in the internal K content. 7. It is concluded that these effects of Li, and their alteration by ouabain, reflect the activity of a mechanism for the active extrusion of Li ions. It is suggested that the mechanism for the active extrusion of Li is the same as that for Na. 8. There also seems to be a site for Li that controls the phosphate efflux and which is half-maximally activated with external Li concentrations of about 2-4 mM.

Animals↗
PubMed1979

The initial heat production in garfish olfactory nerve fibres.

A study has been made of the temperature changes associated with the passage of a single impulse in the non-myelinated fibres of the garfish olfactory nerve: and the time course of these temperature changes has been compared with the time course of the electrical events during the action potential. As in other non-myelinated nerves studied the observed temperature changes result from a biphasic initial heat production consisting of a transient evolution of heat (the positive heat) followed by a rapid heat reabsorption (referred to as the negative heat). There is no evidence of any additional phases of initial heat production. At 0 degrees C the measured positive initial heat is 224 mucal/g impulse (937 muJ/g impulse); and the corresponding negative initial heat is 230 mucal/g impulse (962 muJ/g impulse). The residual initial heat is very small, being about -6 mucal/g impulse (-25 muJ/g impulse). In the range 0-10 degrees C there is no significant effect of temperature on the magnitude of either the positive or the negative phases of heat production. The experimental thermal records were analysed to determine the true time course of the temperature changes in the nerve undistorted by the recording system. The time course of the temperature changes does not fit with that of the transmembrane voltage change as represented by the monophasic compound action potential recorded externally from the same point on the nerve. A better fit is obtained if the temperature changes are compared with the square of the voltage change in accordance with the view that the heat derives almost wholly from free energy changes and entropy changes in the membrane capacity. The best fit is obtained if it is assumed that the membrane potential does not discharge to zero during the action potential but that at the peak of the action potential the charge (and hence the p.d.) across the membrane capacity retains about 24% of its resting value.

Action Potentials↗
PubMed1979

Binding of radioactively labeled saxitoxin to the squid giant axon.

The binding of saxitoxin, a specific inhibitor of the sodium conductance in excitable membranes, has been measured in giant axons from the squid, Loligo pealei. Binding was studied by labeling saxitoxin with tritium, using a solvent-exchange technique, and measuring the toxin uptake by liquid scintillation counting. Total toxin binding is the sum of a saturable, hyperbolic binding component, with a dissociation constant at 2--4 degrees C of 4.3 +/- 1.7 nM (mean SE), and a linear, nonsaturable component. The density of saturable binding sites is 166 +/- 20.4 micrometers-2. From this density and published values of the maximum sodium conductance, the conductance per toxin site is estimated to be about 7 pS, assuming sequential activation and inactivation processes (F. Bezanilla & C.M. Armstrong, 1977, J. Gen. Physiol. 70:549). This single site conductance value of 7 pS is in close aggreement with estimates of the conductance of one open sodium channel from measurements of gating currents and of noise on squid giant axons and is consistent with the hypothesis that one saxitoxin molecule binds to one sodium channel.

Animals↗
PubMed1979

Phosphate efflux and oxygen consumption in small non-myelinated nerve fibres at rest and during activity.

1. The oxygen consumption and the movements of labelled phosphate were measured in garfish olfactory nerve at rest and during activity.2. In solutions with 2.5 mM-K and 0.2 mM-phosphate the resting oxygen consumption was 0.206 m-mole/kg.min; activity at 2 sec(-1) produced an extra oxygen consumption of 2.46 mumole/kg.impulse. The extra oxygen consumption declined exponentially with a time constant of 2.62 min at 22-26 degrees C.3. The phosphate efflux, measured simultaneously, had a resting efflux rate constant of 1.24 x 10(-3) min(-1); activity at 2 sec(-1) produced an extra fractional loss of 9.38 x 10(-6) impulse(-1). The increase in phosphate efflux followed almost the same time course as the increase in oxygen consumption.4. Increasing the frequency of stimulation from 2 sec(-1) to 3 or 5 sec(-1) decreased both the extra oxygen consumption and the extra fractional loss of phosphate. When the frequency was decreased to 0.5 or 1 sec(-1) the extra oxygen consumption per impulse increased, while the extra phosphate liberation was lowered.5. Changing the phosphate concentration did not much affect the extra oxygen consumption; on the other hand, lowering or increasing the phosphate from the standard 0.2 mM decreased both the resting and the stimulated phosphate efflux.6. Lowering the K from the standard 2.5 mM did not affect the extra oxygen consumption, but increased both the resting and the extra loss of phosphate. At higher K concentrations the extra oxygen consumption and the extra fractional loss of phosphate decreased without much change in the resting phosphate efflux.7. Application of 1-20 muM-strophanthidin produced a transient decrease in the resting phosphate efflux without much change in resting oxygen consumption. With 10 or 20 muM-strophanthidin the extra fractional loss of phosphate and the extra oxygen consumption were both lowered in approximately the same proportions.8. The findings are consistent with the hypothesis that the increase in intracellular inorganic phosphate that results from increased break-down of ATP after activity, is the main cause for the increased phosphate efflux. A fraction of the increase in intracellular phosphate only appears to be liberated to the outside, the value of the fraction depending on the resting phosphate efflux before activity.9. The initial increase in intracellular inorganic phosphate after an impulse, estimated from the oxygen consumption or the phosphate fluxes, appears to be about 12-19 mumole/kg nerve, remarkably close to the value known from chemical analysis.

Animals↗
PubMed1979

A quantitative description of membrane currents in rabbit myelinated nerve.

1. Voltage-clamp studies were carried out on single rabbit myelinated nerve fibres at 14 degrees C with the method of Dodge & Frankenhaeuser (1958). 2. A method was developed to allow the ionic currents through the modal membrane to be calibrated exactly under voltage-clamp conditions by measuring the resistance of the internode through which the current was injected. 3. The ionic currents in a rabbit node of Ranvier can be resolved into two components, a sodium current and a leak current. Potassium current is almost entirely absent. 4. The sodium currents in rabbit nodes were fitted by the Hodgkin-Huxley model using m2h kinetics. The kinetics of sodium currents in a rabbit node differ from that in a frog node under similar experimental conditions in two respects: (a) inactivation is faster, tau h for rabbit being 2-3 times smaller around -50 mV; (b) the P(Na) (E) curve for mammal is shifted 10-15 mV in the hyperpolarizing direction. 5. From the kinetics of sodium current, the non-propagating rabbit action potential was reconstructed at 14 degrees C. The transient inward sodium current is responsible for the fast initial depolarization phase of the action potential, while the repolarizing phase is accounted for by leak alone. The computed shape of the action potential was in good agreement with the experimentally obtained action potential. 6. At 14 degrees C, frog and rabbit nodes with similar diameters have similar measured gNa values.

Action Potentials↗
PubMed1979

The recovery heat production in non-myelinated garfish olfactory nerve fibres.

1. The recovery heat production of the non-myelinated fibres of garfish olfactory nerve has been measured. 2. At about 20 degrees C the total recovery heat was 381 +/- 26 microcal g-1 impulse-1 at a stimulation frequency of 2 sec-1. 3. The time constant of decay of the recovery heat production after a brief period of stimulation was 78.7 +/- 3.1 sec at about 20 degrees C. 4. Changing the temperature (by +/- 5 degress C) had little effect on the total recovery heat produced. 5. However, lowering the temperature reduced both the rate of rise, and the maximum rate of recovery heat production whereas the time constant of decay was increased. Raising the temperature produced corresponding changes in the opposite direction. 6. the recovery heat production measured in the present experiments is consistent with the previously measured oxygen consumption in the same preparation.

Animals↗