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Biomedical subjects

J Dudel

Publications and source records attributed to J Dudel.

At least 109 records · Page 6Linked to original sources
PubMed1982

Neurotransmitter release and its facilitation in crayfish. III. Amplitude of facilitation and inhibition of entry of calcium into the terminal by magnesium.

Excitatory postsynaptic currents (EPSCs) were recorded extracellularly from synaptic spots on crayfish opener muscles. Release of transmitter was determined by counting the average number of quanta which appear after a stimulus. When [Mg]0 was increased from 2.5 to 12.5 mM, release was inhibited. Quantitatively the effect of [Mg]0 could be described by a competitive inhibition of the entry (not of the release) of Ca2+ after an impulse, with apparent dissociation constants KMg between 1.4 and 18 mM [Mg]0, assuming saturation kinetics for entry of Ca2+ and release. At constant [Ca]0, twin pulse facilitation (Fs) for short intervals (about 10 ms) increased when [Mg]0 was raised from low values, reached a maximum at a certain [Mg]0(F) and unexpectedly decreased again at higher [Mg]0. At higher [Ca]0, [Mg]0(F) shifted to higher values. This maximum of facilitation is predicted qualitatively by our theoretical model. However, the amplitude of facilitation was larger than predicted theoretically, and the [Mg]0(F) were smaller than predicted. The theoretical possibilities to correct these discrepancies within the framework of 'residual calcium' based facilitation and saturation kinetics of entry and release were analyzed, but all were in conflict with experimental findings. It is concluded that an essential element is missing in the present theory of facilitation.

Animals↗
PubMed1982

Neurotransmitter release and its facilitation in crayfish. IV. The effect of Mg2+ ions on the duration of facilitation.

Excitatory synaptic currents (EPSCs) were recorded extracelularlly from synaptic spots on crayfish opener muscles. The decay of facilitation after a first pulse was measured by a second pulse given at increasing intervals; the duration of facilitation TF was the interval after which the second EPSC had 1.1 times the amplitude of the first one. Increasing [Mg]0 in the range from 0.5-12.5 mM at low [Ca]0 (1.7-4.5 mM) led to a monotonic prolongation of facilitation. TF showed a S-shaped dependence on [Mg]0, rising very steeply at 2-5 mM [Mg]0. At higher [Ca]0, and also at half normal [Na]0, an increase of [Mg]0 did not affect the decay of facilitation appreciably. As shown before, the decay of facilitation is due to two Cai-removal processes, R1 and R2. Mg0 inhibits only the R1 process, which is also inhibited by high [Ca]0, is dependent on normal [Na]0 and has the characteristics of a Cai in equilibrium with Na0 exchange. As one possible mechanism, competition of Mg0 with Na0 at the extracellular loading site of the exchange is discussed quantitatively.

Animals↗
PubMed1981

The effect of magnesium on the time course of facilitation at the crayfish neuromuscular junction.

Synaptic currents (EPSCs) were recorded extracellularly from single junctions. Pairs of EPSCs were elicited at different intervals, the increase of amplitude of the second one facilitation. Elevated Mg concentrations reduced the amplitude of the EPSC and prolonged facilitation. Also, if the amplitude of the EPSCs at high Mg is made the same as in the control, by raising [Ca]0, facilitation is still prolonged. It is concluded that Mg inhibits not only the entry of Ca into the nerve terminal but also its removal.

Animals↗
PubMed1981

The effect of reduced calcium on quantal unit current and release at the crayfish neuromuscular junction.

Excitatory postsynaptic currents (EPSCs) were recorded extracellularly from large muscle fibers by means of 'patch clamp' electrodes. Compared to usual extracellular recordings, better signal/noise ratio and temporal stability were achieved. In the range of extracellular calcium concentrations [Ca]0 between 2.7 and 13.5 mmol/l (normal), the average amplitude of the EPSC increased more than proportional to [Ca]0. The unit quantum current, C1, and the average release rate, m, were determined from EPSCs and also from spontaneous sEPSCs, using both Poisson and binomial statistics. The main effect of [Ca]0 was on m: at different synaptic sites m depended on the second to fourth power of [Ca]0. In terms of binomial parameters, the release probability p is the [Ca]0-dependent one. In addition, reduction of [Ca]0 from 13.5 to 2.7 mmol/l decreased the unit quantum C1 consistently to 60%; simultaneously the rise and decay of EPSCs and sEPSCs were shortened by 10-20%. [Ca]0 thus has strong presynaptic effects on the release probability, but in addition smaller ones on the postsynaptic channel characteristics.

Animals↗
PubMed1980

Inhibitory synaptic channels activated by gamma-aminobutyric acid (GABA) in crayfish muscle.

Small crayfish muscle fibres were voltage clamped and synaptic current elicited by superfused GABA solutions was measured. Analysis of the fluctuations of synaptic current and of relaxations of the current after voltage steps yielded analogous results. The current has two components. The first component is characterized by the opening of synaptic channels with a single channel conductance gamma = 9 pS and an average open time tau = 5 ms, measured at 23 degrees C and - 100 mV. tau depends on the membrane potential, tau E = tau 0 x eE/epsilon, and epsilon was about +100 mV in the average. The channel open time agrees with the time constant of decay of the inhibitory postsynaptic current (IPSC) elicited by a nerve stimulus. The current is carried by chloride ions. The second current component is much slower, the average channel open time was tau s = 33 ms at 23 degrees C and -60 mV. The open time tau s of the slow component also was shortened on hyperpolarization. The reversal potential for the current component was more positive than -50 mV. This slow component also seems to be a synaptic one.

Animals↗
PubMed1980

Closing of membrane channels effected by gamma-amino-butyric acid (GABA) in crayfish muscle.

In a small crayfish muscle fibers current elicited by superfusion of GABA was studied. In the majority of the fibers the GABA induced synaptic current relaxed after voltage steps in agreement with the known voltage and time dependence of the inhibitory chloride channels. In about 20% of the preparations, however, at low GABA concentrations of 5-50 mumol/l an anomalous i--response occurs, namely a reduced total membrane conductance in response to GABA. This i--response can be described by a closing of membrane channels, in which the average closed time increases on hyperpolarization. Equivalent conductance reductions are also observed in measurements of the power spectral density of the current noise. In addition to the noise spectrum of the inhibitory chloride current (Dudel et al. 1980), a spectrum with a higher value of the corner frequency appeared, which seems to represent the i- component. In contrast to the inhibitory chloride current, the i--response is not blocked by picrotoxin. The receptors and channels which mediate the i--response thus seem to be different from those of the inhibitory iCl. Several lines of evidence indicate that the i--response is due to the closing of potassium channels. The i--response counteracts the inhibitory effect of GABA at low GABA concentrations and can distort the dose-response curve.

Animals↗
PubMed1979

A conductance decrease after application of GABA to crayfish muscle fibers.

Relaxations after voltage steps of membrane current elicited by superfusion with low concentrations of GABA (up to 50 mumol/l) were measured. In many preparations, a conductance decrease due to GABA was observed. The response to GABA was shown to consist of two major components: the well known opening of synaptic chloride channels, and the closing of previously open channels, presumably permeable to K+ ions. The latter component could not be blocked by picrotoxin.

Animals↗
PubMed1979

The voltage dependence of the decay of the excitatory postsynaptic current and the effect of concanavalin A at the crayfish neuromuscular junction.

In voltage clamped crayfish muscle fibers the time constant tau of decay of the EPSC was measured at different clamp potentials E. At 6 degrees C, the average potential dependence of tau is described by tau = 2.3 ms.eE/328 mV. tau was shorter in fast fibers than in slow ones. Concanavalin A supressed the potential dependence by tau, resulting in an increase in tau compared with the control, especially at high negative potentials.

Animals↗
PubMed1977

Voltage dependence of amplitude and time course of inhibitory synaptic current in crayfish muscle.

The membrane of small crayfish muscle fibers was clamped to potentials between-150 and -20 mV and amplitude and time course of inhibitory postsynaptic currents (IPSCs) were studied. The IPSCs were recorded extracellularly by means of a focal microelectrode and also as total clamp current. The IPSCs lasted about 40 ms and were slowed by depolarization. The rate constant alpha of decay of the IPSC depended on membrane potential E according to the relation alpha= 44 s-1 -e-8.7 V E at 13.5 degrees C. alpha increased with temperature with a Q10 of 1.9 to 2.5. The amplitude iI of the IPSC depended nonlinearly on E and decreased with time after a potential shift. This was partly due to movement of Cl--ions, the difference (E--EI) between clamp potential and reversal potential for the IPSC decreasing to a few mV within several minutes after a shift in E. The inhibitory conductance gI increased up to 30-fold for 100 mV depolarization also changed with time. However, the the inhibitory permeability PI proved to be independent of membrane potential and time. The potential dependence of gI is thus largely due to changes in the internal Cl--concentration.

Animals↗
PubMed1977

Aspartate and other inhibitors of excitatory synaptic transmission in crayfish muscle.

Synaptic currents were measured in voltage clamped crayfish muscle fibers which were triggered either by stimulation of the motor axon (EPSC), or by L-gutamate (gEPSC) applied by microiontophoresis or superfusion. Among a number of analogues of glutamate, L-glutamic-acid-gamma-methyl ester, L-glutamic-acid-dimethyl ester and L-aspartate, were reasonably specific antagonists at the motor synapses, although at relatively high concentrations. Aslo, 2-amino-4-phosphono-butyric acid and morphine were effective antagonists; the action of morphine, however, seemed to be unspecific. Aspartate was further shown to decrease the size of the quantum EPSC, without affecting the probability of release of transmitter or the potential change recorded from the presynaptic nerve terminal. The results also indicate that aspartate, after longer incubations, is released as a false transmitter. The dose-response curve to short glutamate pulse is shifted by aspartate to higher glutamate concentrations, without affecting the steep slope of the dose-response curve or the saturation level. This effect can be interpreted as competitive inhibition by aspartate, with an equilibrium concentration of aspartate at the receptor of 0.3--1.5 mmol/l. In longer glutamate applications the receptor desensitizes rapidly. Aspartate reduces this desensitization in addition to its competitive inhibitory effect. Suppression of desensitization can be more effective than inhibition in long glutamate applications; in this case aspartate apparently potentiates the effects of glutamate.

Aspartic Acid↗
PubMed1977

Dose-response curve of glutamate applied by superfusion to crayfish muscle synapses.

Single muscle fibers were space clamped to a membrane potential of -75 to -80 mV, and the synaptic currents elicited by L-glutamate (gEPSCs) were recorded. The bathing solutions flowing across the fibers at high speed could be switched rapidly and repeatedly through valves actuated by solenoids. Glutamate solutions were applied for periods of 7 s or 1 s, and the responses to repeated applications were averaged. For glutamate concentrations of 10-50 mumol/l, applied for 7 s, the gEPSCs reached a steady state. In this concentration range the amplitude of the gEPSC rose steeply proportional to the power n=2.5 to n=6 (average of 12 experiments n=4.0) of the glutamate concentration. At higher concentrations, after rising for a few seconds the gEPSC was reduced by desensitization. At 500 mumol/l glutamate complete desensitization was reached with an approximate time constant of less than 1 s. The glutamate concentration that elicited a half maximum gEPSC was K=70 mumol/l. If glutamate was superfused only for 1 s, similar dose-response curves were observed. In these experiments n was between 4 and 6. The results obtained by superfusion agree quantitatively with those published for electrophoretic applications.

Animals↗
PubMed1976

Four types of GABA receptors in crayfish leg muscles characterized by desensitization and specific antagonist.

The effects of application of GABA were studied in the closer and stretcher muscle of crayfish walking legs and compared to those on the opener muscle. EPSPs were measured intracellularly and extracellularly at single synaptic spots, and the input resistance of the muscle fiber was determined. In contrast to the opener muscle, in the closer and stretcher GABA receptors desensitized nearly completely within 5-10 min in the presence of GABA. The presynaptic receptors desensitized more slowly than the postsynaptic ones. While in the opener muscle betaguanidino propionic acid (betaGPA) activates only the presynaptic GABA receptors, in the closer and stretcher muscles both the pre- and the postsynaptic receptors are activated by betaGPA. The postsynaptic GABA receptor on the closer muscle desensitizes in the presence of betaGPA. The results show that with respect to desensitization and the effect of betaGPA four types of GABA receptors can be distinguished. As far as is known from the literature, the homologous synapses in lobster and crab can be assumed to have the same receptor types as those found in crayfish.

Aminobutyrates↗
PubMed1975

Potentiation and desensitization after glutamate induced postsynaptic currents at the crayfish neuromuscular junction.

Glutamate was applied iontophoretically in short (10 to 20 ms) pulses through micropipettes of 10 to 30 M Omega resistance to synaptic spots on crayfish muscle fibres. The resulting glutamate induced postsynaptic currents (gEPSCs) were measured using a voltage clamp of the muscle fiber. Dose-response curves for the action of glutamate were constructed summing g-EPSCs elicited by two separate iontophoretic pipettes at the same synapse. The dose-response curves showed a log log slope of 2, the g-EPSC rising with the second power of the glutamate concentration. Following a small conditioning g-EPSC with delay of up to 1 s, a second g-EPSC was potentiated. For short delays maximum potentiation was 3-fold. For large g-EPSCs potentiation gave way to desensitization: following a large conditioning gEPSC a second one was reduced for delays of up to several seconds. Possible mechanisms of potentiation and desensitization are discussed.

Animals↗
PubMed1975

Kinetics of postsynaptic action of glutamate pulses applied iontophoretically through high resistance micropipettes.

Glutamate induced postsynaptic currents (g-EPSCs) were elicited by 2-5 ms glutamate pulses applied iontophoretically through high resistance (80-200 M Omega) micropipettes. Such g-EPSCs decayed with time constants in the range of 5 ms. The dose-response curves for the action of glutamate were S-shaped with a limiting log log slope of 4-6, the half maximum response concentration of glutamate was about 10(-4) Mol/l and the maximum synaptic current in the range of 30 nA. In pairs of small g-EPSCs following each other with delays between 3 and 100 ms, the second one was potentiated. For short delays potentiation was up to 60 fold. The time course of the g-EPSCs and of their potentiation can be described quantitatively with the following assumptions: 1. The simultaneous reaction of 4-6 glutamate molecules with a receptor triggers postsynaptic current flow. 2. The synaptic glutamate concentration is determined by diffusion from a point source. 3. Potentiation is due to summation of the synaptic glutamate concentrations generated by pulse 1 and by pulse 2. The relevance of these results for the interpretation of the natural EPSC is discussed.

Animals↗