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Biomedical subjects

C Franke

Publications and source records attributed to C Franke.

At least 127 records · Page 7Linked to original sources
PubMed1989

Chloride channels gated by extrajunctional glutamate receptors (H-receptors) on locust leg muscle.

Outside-out patches of extrasynaptic membrane were isolated from leg muscles of locusts. L-Glutamate and its agonists were applied to such patches either continuously or in rapidly switched pulses. When the pipette contained a high chloride concentration, 2.5 x 10(-5) M glutamate triggered single-channel currents (gated by H-receptors) with a conductance of 25 pS which were carried by chloride, in addition to cationic channels (gated by D-receptors). For the chloride channels, the distribution of channel open times had components of about 2 and 12 ms. Pulses of higher glutamate concentrations elicited many superimposed channel openings, and the approximately saturating concentration of 10(-3) M glutamate opened 100-200 channels simultaneously. When the pipette contained low chloride, channel conductance was reduced, and the current voltage relation was shifted towards the now negative chloride equilibrium potential. H-Receptor-gated chloride channels were activated by glutamate, ibotenate and aspartate, but not by GABA, quisqualate, kainate, N-methyl-D-aspartate and carbachol. The currents declined in the continued presence of agonist showing a time constant of desensitization greater than 1 s. Recovery from desensitization after removal of the agonist was tested with double pulses and was found to have a time constant of about 300 ms.

Animals↗
PubMed1989

Argiopine blocks glutamate-activated single-channel currents on crayfish muscle by two mechanisms.

1. The effect of the spider venom argiopine on L-glutamate-activated membrane channels of crayfish muscle was investigated using the patch-clamp technique. 2. When 10(-2) M-glutamate and 10(-9) M-argiopine were contained in the pipette solution of a cell-attached patch, bursts of openings of excitatory channels appeared after formation of the patch. These bursts ceased abruptly after variable periods of time in the range of 5 min. Higher concentrations of argiopine (up to 10(-6) M) blocked more rapidly, approximately in proportion to concentration. 3. The block of excitatory channels could be partially or completely reversed by hyperpolarizing the membrane by up to -190 mV from the resting potential. The time constant of the recovery of channel opening decreased with increasing hyperpolarization and was 2 ms with -160 mV hyperpolarization. Switching back from the hyperpolarized level to the resting potential, the time constant for the resulting block was about 3 s (10(-7) M-argiopine). Potential-dependent block by argiopine with similar characteristics was also observed in outside-out patches. 4. Up to argiopine concentrations of 10(-7) M the kinetics of channel openings and of bursts measured in pre-block periods or during reversal of the block by hyperpolarization were indistinguishable from controls. 5. When the potential-dependent block observed in the presence of 10(-6) M-argiopine and 10(-2) M-glutamate was reversed by hyperpolarization, additional short closings occurred during bursts. This 'flickering block' did not change burst length appreciably, but an additional open time component (tau = 0.1 ms) appeared and the average open time per burst was reduced. 6. At least two reaction steps seem necessary to model the behaviour of the potential-dependent block. The flickering block may be described as intermittent blocking of the channel which does not interfere with the reactions between glutamate and the channel.

Animals↗
PubMed1989

[Development of a rational monitoring strategy for workers exposed to tetrachloroethylene].

A 5 year follow-up of 130 workers exposed to tetrachlorethylene (dry cleaning) was performed, including measuring of exposure conditions (personal dosimetry, exposure tests) and clinical investigations. No signs of hepatoxicity of tetrachlorethylene could be detected, but slight derangements of nerval functions may develop in long-term exposed workers. Nerve motor and sensory conduction velocity shows a tendency to diminution. Recommendations are derived for biological monitoring and health surveillance of workers exposed to tetrachlorethylene.

Air Pollutants, Occupational↗
PubMed1988

Rapid activation and desensitization by glutamate of excitatory, cation-selective channels in locust muscle.

Outside-out patches of membrane were excised from extensor tibiae muscles of locusts. L-Glutamate or its agonists were applied to such patches in short pulses by means of a lipid filament switch. Cationselective, excitatory channels were activated by quisqualate, L-glutamate and aspartate (in decreasing order of effectivity), but not by ibotenate, kainate, N-methyl-D-aspartate and glycine. At high agonist concentrations, channel activation reached a peak within 1 ms. Two kinetic types of channels have been identified: L-channels with on average relatively long and S-channels with short openings. Both types of channel openings showed surprisingly high rates of desensitization, channel activity declining after the initial surge to zero with time constants of about 25 and 3 ms, respectively. The L-channels exhibit open times close to those of channels recorded in M omega-seal studies. The S-channel has not been reported previously.

Animals↗
PubMed1988

Ionic permeabilities of L-glutamate activated, excitatory synaptic channel in crayfish muscle.

Excitatory single channel currents triggered by L-glutamate were measured in outside-out excised patches of crayfish muscle membrane. If an 'intracellular' solution was present in the pipette and normal extracellular solution with added glutamate (10(-3) M) passed the outside of the patch, the single channel currents, i1, had amplitudes of -8 pA at a patch potential of -70 mV. If in the extracellular solution Na+ was replaced by Li+ or Ca2+, the amplitudes of single channel currents were reduced by about 30%. Only about 20% of the channel current amplitude remained on replacement of Na+ by choline. Replacement of Na+ reduced the variance of channel amplitude distributions to the level of the baseline. Presence of Na+ thus induces an additional variance of open channel current. When the proportions of Na+/choline were varied, the resulting channel currents could be separated in Na+, Ca2+ and choline components. The amplitude of the Na+ component, i1,Na, could be described by a constant channel permeability pi Na = 110 10(-15) cm3 s-1 according to the constant field equation. Ba2+ could replace Ca2+ without change in single channel current, while replacement of Ca2+ by Mg2+ reduced the channel currents by 20%. The following permeabilities of the single channel were estimated (in 10(-15) cm3 s-1): pi Na = 110, pi K = 86, pi Ca = 30, pi Mg = 24, pi Ba = 30, pi Li = 84 and pi choline = 11. These permeabilities were obtained inserting ionic concentrations. The respective permeabilities are listed also as calculated on the basis of ionic activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Calcium dependent gating of the L-glutamate activated, excitatory synaptic channel on crayfish muscle.

Excitatory, glutamate-activated single channel currents were measured in outside-out patches of crayfish muscle. The open times of single channel openings, and the durations and rates of bursts were evaluated. These kinetic parameters were not appreciably affected by replacement of extracellular Na+ by Li+ or choline. Changes in extracellular Ca2+ concentration Cao also did not influence the duration of single openings. However the mean burst duration decreased for Cao less than 13.5 mM and the rate of bursts declined with a power of almost 2 in low Cao. At Cao less than 1 mM practically no channel openings were observed in presence of glutamate. In order to exclude more rapid desensitization of the glutamate receptors in low Cao as the cause of disappearance of channel openings, glutamate was applied in short pulses with a liquid-filament switch. In 0 Cao also a glutamate pulse did not trigger channel openings. In presence of 13.5mM Cao, the inorganic Ca-channel blockers La3+ and Cd2+ diminished the duration and rate of bursts of channel openings in a similar manner as low Cao. The effects of low Cao and of Cd2+ were tested also on quantal postsynaptic currents, EPSCs, which were recorded through a perfused macro-patch-clamp electrode. At 1.4 mM Cao in the perfused electrode tip, spontaneous EPSCs were reduced at least by a factor of 4, and elicited EPSCs by a factor of 16. Application of Cd2+ had similarly strong effects on the EPSCs. Also the decay of EPSCs was shortened substantially in 1.4 mM Cao or 5 mM Cd2+. The inhibitory Cl(-)-channel of crayfish muscle, activated by glutamate or GABA, also was studied in outside-out patches. The openings of this channel persisted in 0 Cao solutions; the block of channel openings in low Cao thus is a specific property of the excitatory channel. The action of Cao on the excitatory channel may be described as that of a cofactor to glutamate. A possible reaction scheme is proposed.

Animals↗
PubMed1988

[Thrombus fragmentation and local lysis in extensive pulmonary embolisms].

We report on two patients, both with massive pulmonary embolism. One was effectively treated with small local doses of urokinase and mechanical fragmentation of the embolus. In the second case, despite previous ineffective systemic lytic therapy with urokinase, the local treatment with streptokinase and embolus fragmentation led to complete lysis of the emboli.

Aged↗
PubMed1988

[Animal experiment and clinical studies of the use of anti-inflammatory agents in chemical burns of the eye].

In animal experiments and a clinical study of chemically burned eyes the anti-inflammatory effect of topically applied steroids and indomethacin (an inhibitor of cyclooxygenase) was investigated. Both the animal model and the clinical tests indicate the desirability of immediate local application of dexamethasone eyedrops 0.1% under careful biomicroscopic control of the burned eye and with local antibiotics. The use of topical steroids is a part of the authors' treatment for moderately severe and severe chemical eye burns (second degree, beginning third degree). However, this anti-inflammatory therapy cannot be recommended with indomethacin alone, because of the leukotriene-induced, increased infiltration of polymorphonuclear neutrophils and corneal ulceration.

Animals↗
PubMed1987

Liquid filament switch for ultra-fast exchanges of solutions at excised patches of synaptic membrane of crayfish muscle.

A liquid filament switch is described which can exchange the solution passing an excised outside-out patch of postsynaptic membrane within less than 1 ms. Application and washout of transmitter can be repeated at high rates. Results of such rapid activations by glutamate are shown for the excitatory and the inhibitory channel of crayfish muscle. The excitatory channel is activated within less than 0.5 ms, and after an initial peak of openings desensitizes with a time constant of 5 ms to a low steady-state level. A kinetic scheme of these reactions is proposed. The activation of the inhibitory channel is slower, and this channel desensitizes more slowly than the excitatory one.

Animals↗
PubMed1987

Taste receptors in crayfish: recording of single nicotinamide-activated channels.

The patch clamp technique was adapted to chemoreceptive sensory cells in the claw of Austropotamobius torrentium. In cell-attached and in outside-out patches, concentrations of nicotinamide from 10(-6) mol/liter to 5 X 10(-5) mol/liter activated openings of single channels located in the cell body of the sense cell. The characteristics of these single channel openings were similar to those of neurotransmitter activated channels: the I/V curve was approximately linear, showing a reversal potential of about +15 mV and a conductance of about 33 pS. The mean open time was 1-2 ms. A similar concentration dependence was found for the activation of single channel openings as shown previously for the action potential discharge elicited by nicotinamide at the same preparation.

Action Potentials↗
PubMed1987

Single glutamate-gated synaptic channels at the crayfish neuromuscular junction. I. The effect of enzyme treatment.

Single glutamate activated ionic channels were recorded with the patch clamp technique from untreated crayfish muscle fibres with M omega seals, and after treatment with collagenase, with G omega seals. In regions with single channel activity spontaneous synaptic currents could also be recorded, and the channels were therefore identified as synaptic. The single channel current amplitude was -7 to -8 pA at the resting potential of -70 mV, representing a conductance of 100 pS. The amplitudes decreased by a factor of two when the temperature was lowered by 10 degrees C. Openings occurred in bursts, and the mean burst length varied between 0.3 ms (50 microM glutamate in the pipette) and 0.8 ms (1 mM glutamate in the pipette). After treatment with collagenase, G omega seals could be formed. The conductance of the channel and the mean burst length was not affected by the enzyme, but after treatment active spots could be found easier and they were distributed more uniformly along the fibre. After treatment the concentrations of glutamate necessary to elicit channel openings were higher (100 microM compared to 20-50 microM) and simultaneous openings of two or more channels were observed very rarely. Synaptic currents could not be recorded from preparations cleaned by collagenase (2 mg/ml) for longer than 60 min.

Animals↗
PubMed1987

Single glutamate-gated synaptic channels at the crayfish neuromuscular junction. II. Dependence of channel open time on glutamate concentration.

Single, glutamate activated ionic channel currents were recorded from crayfish muscle in the cell attached mode. Different concentrations of glutamate were present in the patch clamp pipette. Bursts of openings were observed with a concentration dependent number of short gaps per burst. Also the mean burst length was concentration dependent and varied between 0.3 ms (100 microM) and 1.3 ms (20 mM). Even with the highest concentrations of glutamate the channel activations were well separated and the beginning and the end of a burst could be defined. The distributions of open times and of burst lengths could be fitted well with a single exponential component for all studied concentrations of glutamate. The distributions of closed times were composed of two or three exponential components (with possibly more than one channel contributing). The mean burst length was compared with the time constants of decay of synaptic currents (0.8-3.0 ms at 19 degrees C) which were measured either with the same pipette as the single channel currents or with a macro patch technique. An estimation of the glutamate concentration at the receptors during synaptic transmission gave values in the millimolar range. The most simple model of glutamate-receptor interaction contains two binding sites for glutamate but no singly liganded open states. Rate constants were estimated for this model.

Animals↗
PubMed1985

High-resolution measurements of single-channel currents activated by glutamate in crayfish muscle.

Patch-clamp pipettes filled with 50-5000 microM glutamate were placed on crayfish muscle fibers treated with collagenase, formed G omega seals and elicited single-channel currents with a main amplitude of about -8 pA at -70 mV membrane potential, representing a conductance of about 100 pS (19 degrees C). Evaluation of the channel openings longer than 1 ms yielded three sublevels of this conductance. The channels opened in bursts, the durations of which were distributed in two exponential components with time constants of about 0.1 and 0.3 ms at low glutamate concentrations, which rose to about 0.4 and 1.8 ms, respectively, at high glutamate concentrations. The distributions of closed times could be described by three time constants which also varied with glutamate concentration. Comparison of the burst durations with the decay time constants of natural synaptic currents indicates effective glutamate concentrations in the millimolar range during transmission.

Animals↗
PubMed1984

Excitability and depolarization-release characteristics of excitatory nerve terminals in a tail muscle of spiny lobster.

In the deep abdominal L1-extensor muscle of the spiny lobster (Panulirus penicillatus) quantal excitatory postsynaptic currents (EPSCs) were recorded through macro-patch-clamp electrodes. Release of transmitter quanta from terminals was also elicited by depolarizing current pulses given through the recording electrode. The majority of terminals were excitable: on increasing the depolarization pulses, release was triggered at a threshold in an all-or-nothing manner. If excitation was blocked by tetrodotoxin (TTX), release was graded with depolarization reaching the amplitude of the all-or-nothing response at pulse amplitudes several times higher than the former threshold level. Some inexcitable terminals were also found: in these, release was graded for increasing depolarization pulses, and TTX did not alter the depolarization-release relation. Among the other types of terminals studied with the same technique, the proportion of excitable terminals in this lobster tail muscle is higher than in the crayfish opener and lower than in the frog's cutaneous pectoris muscle. The contribution of the increase in intraterminal Ca concentration to the control of release was estimated using facilitation of a test EPSC as an indicator of Ca inflow during a preceding depolarization pulse. This facilitation was found to have a maximum at a certain pulse amplitude, PF, and to decline for larger depolarizations. Release, however, rose considerably for depolarizations larger than those effected at PF. It is concluded that, like in crayfish and frog motor terminals, release is controlled directly by depolarization in addition to the control by Ca-inflow.

Action Potentials↗
PubMed1984

Inhibition of human placental progesterone synthesis by danazol in vivo.

In vivo, a single dose of 1000 mg danazol was given orally to pregnant volunteers (n = 8) prior to a therapeutic abortion (8th-12th week of gestation). Changes in serum progesterone and estradiol were evaluated both by analysis of percentage values related to initial concentrations or statistically by a Kruskal-Wallis test comparing absolute steroid concentrations. Following treatment (n = 8), a significant decrease in mean plasma progesterone of about 20% was observed within 2-4 hours; progesterone levels varied between 80-120% during 24 hours in controls (n = 10); individual serum estradiol decreased up to 30% of control values 2 hours after danazol application. Changes in estradiol in controls versus tests were not statistically significant (p less than 0.05) when absolute estradiol concentrations were compared. Only a slight (10-20%) decrease in mean serum DHAS was found between 2 to 6 hours following danazol treatment. This study demonstrates the inhibitory activity of danazol on the human maternal and fetal steroidogenesis in vivo. The possible sites of action of danazol are discussed.

Abortion, Therapeutic↗
PubMed1984

Strengthening of synaptic contacts of an excitatory axon on elimination of a second excitatory axon innervating the same target.

In the deep abdominal extensor muscles of spiny lobsters (Panulirus-pennicillatus), the common excitor axon of segment II was eliminated by intracellular injection of pronase. At 1 to 23 days after the operation, the quantal content of excitatory postsynaptic currents (EPSCs), elicited by stimulation of the specific excitor of the L1 muscle, was determined in a specific area of the L1 muscle, both in the operated and in the contralateral control side. The EPSCs in the operated muscles had about a 5 times higher quantal content compared to those in the controls, the change developing within 1 to 2 days after operation. In camera lucida drawings of preparations stained with methylene blue, increased branching of the remaining excitatory axon was obvious at more than 4 days after the operation. To investigate the possibility of contribution of central mechanisms (Rotshenker, S. (1979) J. Physiol. (Lond.) 292: 535-547). to this effect, the bundle of five axons to the deep abdominal extensors of segment II was cut immediately after injection of pronase into the common excitor axon. This caused a reduction of the quantal content of EPSCs and shrinking of the field of innervation in the operated L1 muscle as compared to the control. Therefore, axonal continuity or central connections seem to be necessary for the development of an increased innervation by the specific excitor to L1 after eliminating the common excitor axon. Possible postsynaptic effects of the elimination of the common excitor axon were controlled by recording synaptic single channel currents elicited by the excitatory transmitter glutamate, using the patch clamp method. These single current events did not show appreciable changes in operated L1 muscles. Therefore, the presynaptic strengthening effect on the nerve terminals of the specific L1 excitor is predominant after elimination of the common excitor axon.

Animals↗
PubMed1983

Single synaptic channels recorded at glutamate sensitive patches on a crayfish muscle.

When a patch clamp pipette filled with 50 mumol/l glutamate was placed on a muscle fiber of the deep abdominal extensor of crayfish, in some locations current pulses were recorded which were identified as synaptic, glutamate-operated ionic channel openings. At a given site all current pulses had approximately the same amplitude. At resting potential and 19 degrees C, their mean amplitudes were 7-8 pA, corresponding to channel conductances of 70-80 pS. The distribution of open times of the channels could be described by the sum of two exponentials with time constants tau 1 of 0.3-0.5 ms for the longer, and tau 2 of 0.03-0.06 ms for the shorter component. Bursts of channel openings interrupted by gaps occurred in about 10% of the events only. The longer time constant tau 1 conforms to the channel open times estimated by noise analysis [11].

Animals↗