PubMed Health⌕ Search

Biomedical subjects

J M Bekkers

Publications and source records attributed to J M Bekkers.

10 recordsLinked to original sources
PubMed1991

The effect of tetrodotoxin on the sodium gating current in the squid giant axon.

The effect of tetrodotoxin (TTX) on the sodium gating current in the squid giant axon was examined by recording the current that flowed at the pulse potential at which the ionic current fell to zero, first in the absence and then in the presence of TTX. The addition of 1 microM TTX to the bathing solution had no consistent effect on the size of the initial peak of the gating current, but resulted in small changes in the timecourse of its subsequent relaxation which were mainly caused by a reduction of about one quarter in the component that has a delayed onset and may possibly arise from changes in the state of ionization of groups in the channel wall when the lumen fills with water. Our findings suggest that the binding of TTX at the outer face of the sodium channel does not interfere with the mechanisms of activation and inactivation by the voltage sensors, but has an allosteric effect on the access of internal cations to the inside of the channel.

Animals↗
PubMed1991

Excitatory and inhibitory autaptic currents in isolated hippocampal neurons maintained in cell culture.

Individual rat hippocampal neurons, grown in isolation from other neurons on small spots of permissive substrate, were studied in order to characterize the electrical properties of the synapses that such cells formed with themselves (autapses). Excitatory (probably glutamatergic) or inhibitory (probably type A gamma-aminobutyratergic) autapses were frequently found. Excitatory autaptic currents reversed near the potential expected for monovalent cations were blocked by the glutamatergic antagonist kynurenic acid, and possessed a slow component with the pharmacological profile of N-methyl-D-aspartate-type channels. These currents also exhibited trial-to-trial statistical fluctuations in their amplitudes, this being well-described by quantal analysis. Inhibitory autaptic currents reversed at hyperpolarized potentials, as expected for chloride-permeable pores and were blocked by picrotoxin, a type A gamma-aminobutyric receptor antagonist. It is concluded that autaptic currents in culture are identical to those found at synapses.

2-Amino-5-phosphonovalerate↗
PubMed1990

Two different ways evolution makes neurons larger.

As evolution makes larger brains it also increases the size of many of the individual neurons that make up the brain. How neurons are made larger can give clues about design principles of the brain's circuits. One way of making a larger neuron is called conservative scaling. If evolution magnifies a particular type of neuron by a factor of two-that is, each dendrite is made twice as long-then the neuron is scaled conservatively if the magnified neuron has dendrites with 4 times the diameter of their unscaled counterparts. This type of scaling leaves the passive cable properties of the neuron unchanged and so maintains a balance in effectiveness between proximal and distal dendritic inputs. One might imagine that, for some types of circuits, maintaining such a balance would be necessary to use just the same neuronal interconnections in both large and small brains. We have compared dentate granule cells and CA1 pyramidal neurons in cat and human to establish how these cell types are, in fact, scaled. Both cell types are larger in human than in cat, even though their general form is conserved. Pyramidal neurons scale conservatively, but dentate granule cells do not. The CA1 circuits seem, then, to require conservation of the passive cable properties of their elements, whereas dentate does not. We suggest that the reason CA1 neurons scale conservatively is that, for this region, each individual synaptic input exerts a significant effect on the cell's output, whereas in dentate the neuronal output represents the average of a large number of anonymous individual inputs.

Animals↗
PubMed1990

Origin of variability in quantal size in cultured hippocampal neurons and hippocampal slices.

The size of synaptic quanta has been found to display considerable variation in cultured hippocampal neurons, but the source of this variability was previously unknown. We have now compared the properties of locally evoked miniature excitatory postsynaptic currents in cultured hippocampal neurons and in thin hippocampal slices using whole-cell patch-clamp recordings. The variability in miniature excitatory postsynaptic current size was similar in both preparations and occurred in cultured neurons when only one or a few synaptic boutons were stimulated. Thus, the variability in miniature excitatory postsynaptic current amplitude is not an artifact of cultured neurons and arises predominantly from variability within a single bouton. Possible origins of this variability are discussed.

Animals↗
PubMed1990

Gating current associated with inactivated states of the squid axon gating channel.

Sodium (Na) channel gating currents were measured in squid (Loligo forbesi) axons to study transitions among states occupied by the Na channel when it is inactivated. These measurements were made at high temporal resolution with a low-noise voltage clamp. The inactivation-resistant gating current, I(g,inact), could be separated into a very fast (tau = 5-25 mus) and a slower (tau = 40-200 mus) component over a wide range of test potentials (-140 mV to 80 mV) and for three different starting potentials (-70 mV, 0 mV, and 50 mV). The time constants for these components plotted against test potential lay on two bell-shaped curves; the time constants at any particular test potential did not depend on the starting potential. Both components had charge-voltage curves that saturated between -150 mV and 50 mV. A fast spike, similar to the fast component of I(g, inact), was also apparent in recordings of the fully recovered total "on" gating current. I(g, inact)(fast) and I(g, inact)(slow) could not together be described by the simplest possible model, a linear three-state scheme; however, I(g, inact)(fast) could be modeled by a two-state scheme operating in parallel with other gating processes. I(g, inact)(slow) and the gating current due to recovery from inactivated states into resting states could together be well described by a three-state scheme. This lends support to models in which a pair of inactivated states are connected by a single voltage-dependent step to the resting states of the Na system.

Animals↗
PubMed1990

Computational implications of NMDA receptor channels.

We have summarized the quantitative relations developed so far for the description of NMDA receptor function. One of the most important gaps in our knowledge relates to desensitization. A full quantitative treatment of computational uses of NMDA receptor channels must await a formalization of this process and also a more detailed examination of the occupation of closed states of the receptor whose binding sites are occupied. As this information becomes available and the role of NMDA receptors in the function of brain circuits is further explored, we should be able to define accurately this second computational mode.

Animals↗
PubMed1989

NMDA and non-NMDA receptors are co-localized at individual excitatory synapses in cultured rat hippocampus.

A CENTRAL assumption about long-term potentiation in the hippocampus is that the two classes of glutamate-receptor ion channel, the N-methyl-D-aspartate (NMDA) and the kainate/quisqualate (non-NMDA) subtypes, are co-localized at individual excitatory synapses. This assumption is important because of the perceived interplay between NMDA and non-NMDA receptors in the induction and expression of long-term potentiation: the NMDA class, by virtue of its voltage-dependent channel block by magnesium and calcium permeability, provides the trigger for the induction of long-term potentiation, whereas the actual enhancement of synaptic efficacy is thought to be provided by the non-NMDA class. If both receptor subtypes are present at the one synapse, such cross-modulation could occur rapidly and locally through diffusible factors. By measuring miniature synaptic currents in cultured hippocampal neurons we show that the majority (approximately 70%) of the excitatory synapses on a postsynaptic cell possess both kinds of receptor, although to different extents. Of the remaining excitatory synapses, approximately 20% contain only the non-NMDA subtype and the rest possess only NMDA receptors. This finding provides direct evidence for co-localization of glutamate-receptor subtypes at individual synapses, and also points to the possibility that long-term potentiation might be differentially expressed at each synapse according to the mix of receptor subtypes at that synapse.

Action Potentials↗
PubMed1986

The conductance and density of sodium channels in the cut-open squid giant axon.

Non-stationary Na current fluctuations in small voltage-clamped patches of cut-open squid giant axon were analysed by an ensemble-average technique to yield the single Na channel conductance gamma Na and the Na channel density in the patch. gamma Na appeared to be voltage independent over the range -30 to +40 mV and had a mean value of 4.4 +/- 1.1 pS in 514 mM-Na/20 mM-Na at 5 kHz band width and temperature between 3.5 and 5.0 degrees C. gamma Na did not change significantly at band widths to 20 kHz. gamma Na in reduced Na solutions, 103 mM-Na/4 mM-Na, at 3.5-5.0 degrees C had a mean value of 1.2 +/- 0.3 pS. Internal solutions containing 50 mM-tetraethylammonium (TEA) depressed both gamma Na and the mean Na currents by roughly the same factor, compared with solutions without TEA. The reduced gamma Na had a mean value of 2.2 +/- 0.7 pS. The mean Na channel density in the standard 514 mM-Na/20 mM-Na solution was estimated to be 180 +/- 100 microM-2. The densities in the other solutions mentioned above were not significantly different from this value.

Action Potentials↗
PubMed1984

The effect of local anaesthetics on the components of the asymmetry current in the squid giant axon.

The effects of local anaesthetics and holding potential on sodium and asymmetry currents were studied in intracellularly dialysed squid giant axons. The asymmetry currents were fractionated into their inactivating and non-inactivating components, and the charge displacements Qi and Qn of the two components were determined for pulse potentials between -20 and +40 mV. The charged local anaesthetic RAD 366, a quaternary derivative of lidocaine, applied internally at a concentration in the dialysis solution of 1 mM, did not change Qn, but reduced Qi about 3-fold. The neutral local anaesthetic benzocaine, applied externally at a concentration in the bathing solution of 1 mM, had effects very similar to RAD 366. It did not change Qn, but reduced Qi and the sodium current about 2 . 5-fold. Unlike local anaesthetics, steady membrane depolarization had essentially equal effects on Qn, Qi and sodium current. Lowering the holding potential from -98 to -60 mV for several minutes reduced all three variables to about half. Models of sodium channel voltage-gating are discussed which implicate both Qn and Qi, and which account for the selective blockage of Qi by sodium inactivation and local anaesthetics.

Action Potentials↗