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D Attwell

Publications and source records attributed to D Attwell.

89 records · Page 5Linked to original sources
PubMed1981

The effects of heart rate on the action potential of guinea-pig and human ventricular muscle.

1. On increasing the stimulation frequency of isolated pieces of guinea-pig ventricular muscle, the resting potential depolarizes, and the action potential duration and amplitude are reduced. On termination of the high frequency train of action potentials, these changes are reversed. 2. The resting potential changes are roughly exponential, with a time constant of the order of 10 sec, and are attributable to K+ accumulation in the extracellular space. They are not explicable in terms of known gating variables. 3. The action potential duration and amplitude recover much more slowly than the resting potential, after a high frequency train (half-time approximately 5 min). The time course of these recoveries is not exponential, and is slower after trains which produce more shortening of the action potential. The slow time course suggests that K+ accumulation is not the main cause of the changes in action potential shape. Furthermore, when a certain depolarization of the resting potential is produced by a high frequency train, there is a greater reduction of the action potential duration than that which occurs when the bathing [K+] is raised to produce the same depolarization (Reiter & Stickel, 1968). This is so even when a gradient of extracellular [K+] is induced in the preparation, to mimic non-uniform K+ accumulation. 4. Similarly, the shortening of the action potential produced by toxic doses or cardiotonic steroids is probably not the result of K+ accumulation. 5. The slow changes of the action potential shape produced by a high frequency train are not attributable to the effects of gating variables, nor (solely) to a rise in the intracellular Na concentration stimulating the electrogenic Na/K pump. The dye 3,3'-diethylthiadicarbocyanine, which blocks the Ca2+-activated K conductance in the erythrocyte, has no significant effect on the shape changes. 6. After a sudden change in heart rate, the QT interval of the human electrocardiogram (e.c.g.) changes slowly to a new equilibrium value. The time course of this change is similar to that of the action potential duration in guinea-pig ventricle following a change in stimulation frequency. These changes of the e.c.g. are probably not due to slow alterations of neural or hormonal factors extrinsic to the heart. In the whole heart, the effects on the ventricular action potential duration of changes in sympathetic or vagal tone, or of circulating catecholamines, can be largely accounted for by the changes of atrial driving frequency they produce.

Action Potentials↗
PubMed1980

Behaviour of the rod network in the tiger salamander retina mediated by membrane properties of individual rods.

1. The spread of electrical signals between rods in the salamander retina was examined by passing current into one rod and recording the voltage responses in nearby rods. Rod network behaviour, measured in this way, was simulated from data on rod membrane properties gathered in voltage-clamp experiments on single isolated rods.2. The network voltage responses to square current pulses became smaller, more transient, and had a longer time-to-peak, for rods further away from the site of current injection. Depolarizing currents produced smaller responses than hyperpolarizing currents of the same magnitude.3. Neighbouring rods and cones were coupled less strongly than neighbouring rods.4. The response of the rod network to current injection was unaffected by 2 mm-aspartate(-), which eliminates transmission from receptors to horizontal cells.5. The input resistance of single isolated rods, measured at the resting potential, varied between 100 and 680 MOmega. The lower values were probably due to damage by the micro-electrodes. Electrical coupling was found to be very strong between the rod inner and outer segments.6. A strong ;instantaneous' outward rectification seen in isolated rods at potentials positive to -35 mV was reduced, but not abolished, by 15 mm-TEA.7. In normal solution, isolated rods exhibited a voltage- and time-dependent current, I(A), whose kinetics were approximated by a single first-order gating variable, and whose activation curve spanned the range between -40 and -80 mV. The time constant for the current varied with voltage and was 60-200 msec between -140 and -40 mV.8. A reversal potential for I(A) could not be found between -140 and -40 mV in normal solution, and the fully activated current, I(A), was approximately voltage-independent, with a magnitude of approximately 0.1 nA over this potential range.9. By several criteria, I(A) behaved as a single inward current activated by hyperpolarization. Pharmacological studies suggest, however, that it is the sum of at least two currents with very similar kinetics.10. Most isolated rods exhibited a very slow (tau approximately 3 sec) increase in net outward current on depolarizing beyond -35 mV. The magnitude of this current varied considerably between cells.11. Assuming that the rod network can be approximated by a square lattice of individual rods, resistively coupled together, the voltage-clamp data on isolated rods were used to predict the response of the network to current injection at one cell. The theoretical and observed network behaviour were in good agreement. The resistance coupling neighbouring rods was estimated to be approximately 300 MOmega. The current I(A) plays a major role in determining the behaviour of the rod network.12. The time-dependent current, I(A), is responsible for the peak-plateau wave form of the response to a bright flash. A current similar to I(A) could also account for the negative propagation velocity of the peak of the dim flash response, through the rod network of the turtle, observed by Detwiler, Hodgkin & McNaughton (1978).

Animals↗
PubMed1979

Synaptic transmission: ion concentration changes in the synaptic cleft.

Currents flowing through the postsynaptic membrane of an active synapse will tend to change the concentrations of ions in the synaptic cleft. Published experimental data are used to predict (a) the sodium and potassium concentration changes in the cleft at the frog neuromuscular junction, and (b) the sodium depletion in the cleft under a Ia synaptic bouton on a cat motoneuron. Significant concentration changes are predicted at both synapses. These changes will contribute to the time dependence of the observed current and will cause the reversal potential of the current to be time dependent. At the frog neuromuscular junction, the time course of the endplate current has been shown previously to depend on the magnitude of the current flowing (at a given potential). We attribute this to changes of the cleft ion concentration. The time dependent changes of the endplate current reversal potential that we predict for the neuromuscular junction are probably too small to be detected. This is because the effects of sodium depletion and potassium accumulation on the reversal potential almost cancel. We predict that near the reversal potential small currents of complex time course will remain, i.e. no true reversl potential exists. Such currents have previously been experimentally. At the cat Ia synapse, the synaptic current is predicted to deplete a significant fraction of the available extracellular sodium ions. Consequently, the magnitude of the synaptic current should be relatively independent of the number of postsynaptic channels activated, and of the membrane potental, as has previously been found experimentally.

Animals↗
PubMed1979

Membrane potential and ion concentration stability conditions for a cell with a restricted extracellular space.

For an isolated membrane, the resting (zero current) potential is stable is the slope conductance is positive, and is unstable if the slope conductance is negative. Recent work suggests that the properties of many preparations are influenced by the presence of an extracellular space that is not in good diffusive contact with the bulk extracellular fluid. Ionic current flow across the membrane changes the ion concentrations in this space. These concentration changes affect the stability of the membrane potential. Even if the slope conductance is negative, the presence of the extracellular space can confer stability on the resting potential. Conversely, even if the slope conductance is positive, the extracellular space can produce instability of the resting potential. Evaluation of the relevant parameters for cardiac Purkinje fibres, from published experimental data, suggests that concentration changes in the extracellular space may play a significant role in determining when an action potential is initiated.

Animals↗
PubMed1979

The steady state TTX-sensitive ("window") sodium current in cardiac Purkinje fibres.

Voltage clamp experiments on isolated sheep Purkinje fibres showed an increase of the steady state outward membrane current, over the potential range -65mV to -15 mV, in the presence of tetrodotoxin (TTX, 3.10(-5 M). This "window" current is considered to be the steady state component of the fast sodium current (INa), resulting from the crossover of the activation and inactivation curves which govern the opening of the sodium channel. TTX had no significant effect on the reversal potential, activation curve, kinetics or instantaneous I-V relationship of the pacemaker current IK2. The window found in these experiments extends to potentials well into the range of the action potential plateau. Consequently small changes of the steady state INa might have large effects on the action potential duration. The effects of TTX and local anaesthetics are discussed in this context.

Action Potentials↗
PubMed1979

The action of salicylate ions on the frog node of Ranvier.

1. The effects of salicylate on the membrane currents in the frog node of Ranvier were investigated. 2. External salicylate slows the falling phase of the action potential, with little effect on the action potential amplitude. 3. External salicylate has no effect on the leak current. 4. Most of the actions of external salicylate can be attributed to a simple incorporation of negative charge into the membrane surface. The h infinity, tau h, tau m and m infinity curves for the sodium current are shifted to more negative potentials, as are the n infinity and k infinity curves for the potassium current. Potassium ion accumulation prevented analysis of the action of salicylate on the time constant of the potassium current kinetics. 5. In addition to the h infinity and tau h curves being shifted to more negative potentials, the shapes of the curves are also changed by salicylate. These shape changes cannot be explained by conventional homogeneous surface charge theory. Possible explanations for these changes are discussed. 6. Internal salicylate has similar effects to external salicylate: the gating variable curves for the sodium current are shifted in the negative direction on the voltage axis, rather than in the positive direction expected if negative charge were added to the inner surface of the nodal membrane. This may be due to salicylate crossing the membrane and binding preferentially to a receptor at the external surface, or might be due to a rise in intracellular calcium concentration following inhibition of oxidative phosphorylation.

Action Potentials↗
PubMed1978

Discrete membrane surface charge distributions. Effect of fluctuations near individual channels.

Each gating mechanism controlling permeability in a membrane may be influenced by only a few charge binding sites on the membrane surface, so that fluctuations in the occupancy of these sites are important. Tow extreme cases arise. (a) The time scale of these fluctuations is much shorter than the gating time constant. Then the gating mechanisms are subject to a rapidly varying electric field. If the gating in the absence of these fluctuations obeys exponential kinetics, so does the gating in the presence of the fluctuations. Changes in surface charge do not simply shift the gating variable curves on the voltage axis, but also change their shape. Such effects are seen experimentally and cannot be explained in terms of conventional surface charge theory. If the activation curve in the absence of any surface charge binding is symmetric about the half-activation point, when some of the surface charge sites are occupied the activation curve is in general asymmetric. (b) The fluctuations occur much more slowly than the gating reaction. There are several pools of channels present with different time constant and activation curves. Again the activation curve is asymmetric about the half-activation point, and its shape is changed by alterations in the surface charge. The kinetics of gating of the whole population of channels are multiexponential.

Binding Sites↗
PubMedDate not supplied

Endfeet of retinal glial cells have higher densities of ion channels that mediate K+ buffering.

A major function of glial cells in the central nervous system is to buffer the extracellular potassium concentration, [K+]o. A local rise in [K+]o causes potassium ions to enter glial cells, which have membranes that are highly permeable to K+; potassium then leaves the glial cells at other locations where [K+]o has not risen. We report here the first study of the individual ion channels mediating potassium buffering by glial cells. The patch-clamp technique was employed to record single channel currents in Müller cells, the radial glia of the vertebrate retina. Those cells have 94% of their potassium conductance in an endfoot apposed to the vitreous humour, causing K+ released from active retinal neurones to be buffered preferentially to the vitreous. Recordings from patches of endfoot and cell body membrane show that a single type of inward-rectifying K+ channel mediates potassium buffering at both cell locations. The non-uniform density of K+ conductance is due to a non-uniform distribution of one type of K+ channel, rather than to the cell expressing high conductance channels at the endfoot and low conductance channels elsewhere on the cell.

Ambystoma↗
PubMedDate not supplied

Electrogenic glutamate uptake is a major current carrier in the membrane of axolotl retinal glial cells.

Glutamate is taken up avidly by glial cells in the central nervous system. Glutamate uptake may terminate the transmitter action of glutamate released from neurons, and keep extracellular glutamate at concentrations below those which are neurotoxic. We report here that glutamate evokes a large inward current in retinal glial cells which have their membrane potential and intracellular ion concentrations controlled by the whole-cell patch-clamp technique. This current seems to be due to an electrogenic glutamate uptake carrier, which transports at least two sodium ions with every glutamate anion carried into the cell. Glutamate uptake is strongly voltage-dependent, decreasing at depolarized potentials: when fully activated, it contributes almost half of the conductance in the part of the glial cell membrane facing the retinal neurons. The spatial localization, glutamate affinity and magnitude of the uptake are appropriate for terminating the synaptic action of glutamate released from photoreceptors and bipolar cells. These data challenge present explanations of how the b-wave of the electroretinogram is generated, and suggest a mechanism for non-vesicular voltage-dependent release of glutamate from neurons.

Ambystoma↗
PubMedDate not supplied

Signal clipping by the rod output synapse.

The properties of synapses between retinal neurons make an essential contribution to early visual processing. Light produces a graded hyperpolarization in photoreceptors, up to 25 mV in amplitude, and it is conventionally assumed that all of this response range is available for coding visual information. We report here, however, that the rod output synapse rectifies strongly, so that only potential changes within 5 mV of the rod dark potential are transmitted effectively to postsynaptic horizontal cells. This finding is consistent with the voltage-dependence of the calcium current presumed to control neurotransmitter release from rods. It suggests functional roles for the strong electrical coupling of adjacent rods and the weak electrical coupling of adjacent rods and cones. The existence of photoreceptor coupling resolves the apparent paradox that rods have a 25 mV response range, while signals greater than 5 mV in amplitude are clipped during synaptic transmission. We predict that the strengths of rod-rod and rod-cone coupling are quantitatively linked to the relationship between the rod response range and the synapse operating range.

Animals↗
PubMedDate not supplied

Arachidonic acid induces a prolonged inhibition of glutamate uptake into glial cells.

Activation of NMDA (N-methyl-D-aspartate) receptors by neurotransmitter glutamate stimulates phospholipase A2 to release arachidonic acid. This second messenger facilitates long-term potentiation of glutamatergic synapses in the hippocampus, possibly by blocking glutamate uptake. We have studied the effect of arachidonic acid on glutamate uptake into glial cells using the whole-cell patch-clamp technique to monitor the uptake electrically. Micromolar levels of arachidonic acid inhibit glutamate uptake, mainly by reducing the maximum uptake rate with only small effects on the affinity for external glutamate and sodium. On removal of arachidonic acid a rapid (5 minutes) phase of partial recovery is followed by a maintained suppression of uptake lasting at least 20 minutes. Surprisingly, the action of arachidonic acid is unaffected by cyclo-oxygenase or lipoxygenase inhibitors suggesting that it inhibits uptake directly, possibly by increasing membrane fluidity. As blockade of phospholipase A2 prevents the induction of long-term potentiation (LTP), inhibition of glutamate uptake by arachidonic acid may contribute to the increase of synaptic gain that occurs in LTP. During anoxia, release of arachidonic acid could severely compromise glutamate uptake and thus contribute to neuronal death.

Animals↗