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D Attwell

Publications and source records attributed to D Attwell.

9 recordsLinked to original sources
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↗