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Biomedical subjects

A Duval

Publications and source records attributed to A Duval.

At least 37 records · Page 2Linked to original sources
PubMed1993

The benzodiazepine midazolam preferentially blocks inactivated Na channels in skeletal muscle fibre.

The effects of the benzodiazepine midazolam were studied on frog skeletal muscle fibres held under current- or voltage-clamp conditions. Midazolam induced a concentration-dependent (10(-5) mol/l to 10(-3) mol/l) block of the action potential and of the underlying Na current. Block of the Na current occurred without any changes in its voltage dependence or in its activation and inactivation kinetics. An apparent dissociation constant of 223 mumol/l was determined for midazolam from the rested Na channels of well polarized fibres. The blocking effect of a threshold concentration (10(-5) mol/l) could be greatly enhanced (up to the complete suppression of the current) by predepolarizations, positive holding potentials or high stimulation frequencies. This apparent voltage- and frequency-dependent block (no use dependence, i.e., no activation block) could be ascribed to a blockade of inactivated Na channels. From the apparent shift towards negative potentials of the steady-state inactivation curve, a dissociation constant of 6.0 mumol/l was calculated for midazolam from the inactivated Na channels, according to the modulated-receptor model. These results show that midazolam preferentially blocks inactivated rather than rested Na channels, and suggest that this mechanism of action might contribute to the well-known myorelaxant effect of the benzodiazepines.

Animals↗
PubMed1992

A macro cell-attached patch-clamp study of the properties of the Na current in the vicinity of the motor endplate region of frog single interosseal skeletal muscle fibres.

A macro cell-attached patch-clamp technique using large (16 microns) electrodes was developed to study the properties of the Na current (INa) in the motor endplate region of frog interosseal muscle fibres (resting potential approx.-99 mV). The fibre isolation procedure allows the formation of gigaOhm seals and thus a good voltage-clamp control of the patch. At 22 degrees C, in the presence of 110 mM external [Na] and of K channel blockers, INa activates at -49.6 +/- 1.9 mV, reaches a maximum of 4.33 +/- 0.66 mA/cm2 at -7.5 +/- 2.5 mV and reverses at Vrev equal to +63.2 +/- 1.9 mV. There is no evidence for the presence of a tubular INa. When the [Na] in the recording pipette is changed, Vrev exactly follows the Nernst equation for Na ions. An internal [Na] of 9.69 mM is determined. The Na conductance is maximum (63.56 +/- 7.03 mS/cm2) at +8.9 +/- 3.0 mV and markedly decreases for potentials positive to +25 mV. In contrast, the Na permeability (maximum of 6.13 +/- 0.95 x 10(-4) cm/s at +51.4 +/- 5.6 mV) remains more constant at positive potentials. The Na channels are half-inactivated at -68.9 mV and half-activated at -37.9 mV. At the potential at which INa is maximum, the half-time of activation is 223.9 +/- 10.5 microseconds, the time to peak 365.7 +/- 13.5 microseconds and the time constant of inactivation 260.7 +/- 11.2 microseconds. The time constant of reactivation at -100 mV is 1.44 +/- 0.19 ms. These and other results show that INa can be adequately studied with this technique.

Animals↗
PubMed1992

Poneratoxin, a new toxin from an ant venom, reveals an interconversion between two gating modes of the Na channels in frog skeletal muscle fibres.

The effects of synthetic poneratoxin (PoTX), a new toxin isolated from the venom of the ant Paraponera clavata, were studied under current- and voltage-clamp conditions in frog skeletal muscle fibres. PoTX induces a concentration-dependent (10(-9) M-5 x 10(-6) M) prolongation of the action potentials and, at saturating concentration, a slow repetitive activity developing at negative potentials. PoTX specifically acts on voltage-dependent Na channels by decreasing the peak Na current (INa) and by simultaneously inducing a slow INa which starts to activate at -85 mV and inactivates very slowly. Both the fast and the slow components of INa are suppressed by tetrodotoxin and reverse at the same potential corresponding to the equilibrium potential for Na ions. The fast component of INa has voltage dependence, activation and steady-state inactivation almost similar to those of the control INa. The voltage dependence of the slow Na conductance is 40 mV more negative than that of the fast one. The results suggest that PoTX affects all the Na channels and that the fast and the slow INa components originate from a possible PoTX-induced interconversion between a fast and a slow operating mode of the Na channels.

Animals↗
PubMed1991

A neosynthesis of sodium channels is involved in the evolution of the sodium current in isolated adult DUM neurons.

Short-term culture of isolated adult dorsal unpaired median (DUM) neurons of the cockroach Periplaneta americana has been used to study the evolution of the sodium current during the time in culture after axotomy and deafferentation treatment. An increase in the maximum peak amplitude of the sodium current recorded under voltage-clamp conditions with the patch-clamp technique in the whole-cell recording configuration, was only observed between 24 h and 72 h (75%) without any modification of the kinetics and the voltage-dependence of the current. A decrease in the level of foetal calf serum in the culture medium reduces the amplitude of the sodium current on all days but does not affect its time-course of development which was on the contrary completely abolished by both protein synthesis inhibitors, actinomycin D and cycloheximide. The results obtained in these neurons strongly suggest that a neosynthesis of sodium channel proteins is involved in the evolution of the sodium current induced by axotomy and deafferentation.

Action Potentials↗
PubMed1991

Poneratoxin, a novel peptide neurotoxin from the venom of the ant, Paraponera clavata.

1. At concentrations varying from 10(-8) to 10(-6) M synthetic poneratoxin (PoTX) is a strong, but very slowly acting agonist for smooth muscles and its blocks synaptic transmission in the insect CNS in a concentration-dependent manner and depolarizes giant interneurons. 2. However, in isolated dorsal unpaired median cells 10(-6) M PoTX causes only a reversible hyperpolarization of about 5 mV. 3. At concentrations from 10(-8) to 10(-6) M PoTX affects the electrical activity of isolated cockroach axons, as well as isolated frog and rat skeletal muscle fibres. 4. PoTX prolongs action potentials and induces slow automatic activity, due to a slow Na(+)-current activation at very negative values of potential and due to slow deactivation.

Action Potentials↗
PubMed1991

Evidence for neurotoxic activity of tat from human immunodeficiency virus type 1.

The human immunodeficiency virus (HIV) genome codes for a trans-activating regulatory protein, tat. Using chemically synthesized tat, it was found that 125I-tat and 125I-tat38-86 specifically bound to rat brain synaptosomal membranes with moderate affinity (K0.5 = 3 microM). Interaction of tat with nerve cells was also revealed by flow cytometry, which showed its binding to rat glioma and murine neuroblastoma cells, using both direct fluorescence with fluorescein isothiocyanate-labeled tat and indirect immunofluorescence assays. This interaction was investigated with electrophysiology using isolated excitable frog muscle fibers and cockroach giant interneuron synapses. tat acted on the cell membrane and induced a large depolarization, accompanied by a decrease in membrane resistance, thereby modifying cell permeability. The neurotoxicity of tat was further demonstrated in vitro, on glioma and neuroblastoma cell growth, as well as by a 51Cr release assay in both tumor cell lines. Interestingly, no hemolytic activity of tat for human erythrocytes was found even when tat was tested at its highly neurotoxic concentration. Experiments in vivo showed that synthetic tat is a potent and lethal neurotoxic agent in mice. The use of tat peptide derivatives showed that basic region from 49 to 57 is necessary and sufficient for binding to cell membranes and toxicity.

Action Potentials↗
PubMed1990

A scorpion venom neurotoxin paralytic to insects that affects sodium current inactivation: purification, primary structure, and mode of action.

A new toxin, Lqh alpha IT, which caused a unique mode of paralysis of blowfly larvae, was purified from the venom of the scorpion Leiurus quinquestriatus hebraeus, and its structural and pharmacological properties were compared to those of three other groups of neurotoxins found in Buthinae scorpion venoms. Like the excitatory and depressant insect-selective neurotoxins, Lqh alpha IT was highly toxic to insects, but it differed from these toxins in two important characteristics: (a) Lqh alpha IT lacked strict selectivity for insects; it was highly toxic to crustaceans and had a measurable but low toxicity to mice. (b) It did not displace an excitatory insect toxin, 125I-AaIT, from its binding sites in the insect neuronal membrane; this indicates that the binding sites for Lqh alpha IT are different from those shared by the excitatory and depressant toxins. However, in its primary structure and its effect on excitable tissues, Lqh alpha IT strongly resembled the well-characterized alpha scorpion toxins, which affect mammals. The amino acid sequence was identical with alpha toxin sequences in 55%-75% of positions. This degree of similarity is comparable to that seen among the alpha toxins themselves. Voltage- and current-clamp studies showed that Lqh alpha IT caused an extreme prolongation of the action potential in both cockroach giant axon and rat skeletal muscle preparations as a result of the slowing and incomplete inactivation of the sodium currents. These observations indicate that Lqh alpha IT is an alpha toxin which acts on insect sodium channels.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1989

Changes in Na channel properties of frog and rat skeletal muscles induced by the AaH II toxin from the scorpion Androctonus australis.

The effects of the mammal toxin II isolated from the venom of the scorpion Androctonus australis Hector (AaH II) were studied under current and voltage clamp conditions in frog (semitendinosus) and rat (fast e.d.l. and slow soleus) skeletal twitch muscle fibres. In both species, AaH II induced a dose-dependent prolongation of the action potential (AP) leading at saturating concentration to APs with long plateaus of about 1.5 s in frog and 5 s in rat e.d.l. and soleus fibres. The concentrations to induce 50% of the maximal effect (K0.5) were 9.1 x 10(-9) M in the frog and 1.4 x 10(-9) M in the rat. AaH II increased the time constants of inactivation of the peak Na current and induced a maintained Na current that was greater in rat e.d.l. and soleus (31.6% of peak current amplitude at -30 mV; K0.5 = 0.8 x 10(-9) M) than in frog (16.5%; K0.5 = 15.5 x 10(-9) M) muscles. Peak and maintained Na currents were TTX-sensitive and had identical threshold and reversal potentials. The half-maximum maintained permeability occurred at a potential 20 mV more positive than the peak permeability. Recovery from inactivation and steady-state inactivation of the inactivating Na current remained unchanged. The maintained current deactivated with normal fast kinetics. The action of the toxin reversed poorly on washout but could be largely removed by conditioning depolarizations more positive than the reversal potential of the Na current. Our results suggest that, in vertebrate skeletal muscle fibres, AaH II affects all the Na channels and are consistent with the hypothesis that the maintained current originates from a reopening of previously inactivated Na channels.

Action Potentials↗
PubMed1985

Changes in the ionic currents sensitivity to inhibitors in twitch rat skeletal muscles following denervation.

Under voltage clamp conditions, using the double mannitol gap technique, ionic currents developed by fast (e.d.l.) and slow (soleus) twitch muscle fibers of the rat were analysed at different times following denervation and the results compared with those obtained in normal cells. In slow fibers, denervation caused the appearance of a new population of TTX-resistant Na+ channels (dissociation constant K2 = 2,800 nM) compared with the normal TTX-sensitive Na+ channels (K1 = 9 nM). This new population of Na channels appeared in 5 days and contributed about 32% of the total Na conductance. Denervated fast fibres developed a slow component in the delayed outward current which was found to be typical of slow innervated muscles. This component appeared 5 to 20 days after nerve section. These changes are associated with modifications of potassium channels' sensitivity for specific inhibitors (TEA and 4-AP). After denervation, the delayed outward current in the two types of muscles becomes resistant to 4-AP whereas TEA, which blocks the total delayed outward current in innervated fibers (dissociation constant of 21.4 mM) becomes more effective in blocking the fast component (dissociation constant of 0.61 mM) and less effective in blocking the slow component in denervated cells. The analysis of the characteristics of the TEA sensitive and TEA insensitive components of the outward current leads to the proposal that these components were related to the fast and to the slow components previously described in fast and slow twitch mammalian skeletal muscles.

4-Aminopyridine↗
PubMed1983

[The HLA-DR determinants in chronic inflammatory rheumatism].

The authors present a study of the incidence of HLA-DR antigens in 113 controls and in a Breton population suffering from chronic inflammatory rheumatism. They found 80 cases of rheumatoid arthritis and found a significant increase incidence of the DR4 antigen in rheumatoid arthritis (54% compared with 19.5%; pc less than 10(-4); RR = 4.8) and a decreased incidence of the DR2 antigen (12.5% compared with 35%; pc less than 10(-2); RR = 0.27). The increased incidence of DR4 does not seem to be related to the presence of rheumatoid factor. Out of the 95 cases of chronic inflammatory rheumatism treated, 33 cases of drug intolerance (cutaneous and/or renal to gold salts or D-penicillamine) were reported. The authors found a decreased incidence of the DR2 antigen in the patients who presented a drug intolerance, which was partially significant in the group of patients with rheumatoid arthritis (p less than 0.04; pc less than 0.3). This is an important argument in favour of the supposed protective role of this antigen.

Adult↗
PubMed1980

Ionic currents in slow twitch skeletal muscle in the rat.

1. The ionic currents in slow fibres isolated from rat soleus muscle have been studied under voltage-clamp conditions with a double sucrose-gap method and the results are compared to those obtained from fast fibres isolated from the iliacus muscle. 2. The mean value of the resting potential in slow fibres is -70 mV. a value 8 mV more positive that the mean resting potential of fast fibres (-78 mV). 3. In slow muscle, a fast inward current which is blocked by tetrodotoxin and which depends on external sodium concentration is presumed to be carried by sodium ions. The characteristics of this current, which are time- and voltage-dependent, are similar to those of the iliacus fibres. From a holding potential at -86 mV, this inward current is maximal (2.6 mA/cm2 +/- 0.3) at +49.1 mV +/- 1.5 (mean +/- S.E. of mean), reverses at +127.3 mV +/- 2.2 (mean +/- S.E. of mean), and its half inactivation occurs at +23.2 mV +/- 0.8 (mean +/- S.E. of mean). 4. The delayed outward current in slow fibres is unchanged by exposure to chloride free solution and has a time course very different from that found in fast fibres. This current reaches an initial peak in 5-10 msec and a second peak or steady level after 40-150 msec. The decay of the outward current is also very different, being ten times slower than that in fast fibres (1500-3000 msec). 5. Analysis of the tail currents reveals the existence of two components of delayed current in slow fibres. The faster component reverses at a potential of 11.3 mV +/- 0.9 (mean +/- S.E. of mean) positive to the holding potential (equivalent to a membrane potential of about -75 mV), in contrast to a reversal potential of 35.4 mV +/- 2.5 (mean +/- S.E. of mean) positive to the holding potential for the slower component (equivalent to a membrane potential of about -51 mV. 6. In L-glutamate solution the characteristics of the inward-going rectification are the same in the two types of muscle.

Animals↗
PubMed1980

Comparison between the delayed outward current in slow and fast twitch skeletal muscle in the rat.

1. A comparison of the delayed outward current of isolated fibres from rat soleus and iliacus muscle has been made using a double sucrose-gap voltage-clamp method. 2. The fast and slow components of the outward current were separated using time constants of the tail currents. The results indicate that in both iliacus and soleus fibres there is a shift in reversal potential which depends on the quantity of current that flows during depolarization. 3. The shift is larger in iliacus than in soleus; it is absent in glycerol-treated muscles. 4. The results obtained in normal and in detubulated fibres show that the shift is due to an accumulation process of potassium ions in the lumen of the T-tubules. 5. In detubulated soleus fibres the outward current is composed of a fast and a slow component, each with the same reversal potential; in detubulated iliacus the slow component is absent. 6. In both types of muscles TEA produces a dose-dependent block of the total outward current. 4-aminopyridine has different effects; it inhibits the total outward current in iliacus fibres and only the fast component in soleus fibres. 7. These results show that in soleus fibres a fast and a slow component participate in the potassium outward current, while only a fast component is present in iliacus muscle.

Aminopyridines↗
PubMed1980

[Electromyography of the leg. Study during various segmental movements].

Using anatomical landmarks as fixed points, the authors have squared the cutaneous surface ot the leg into areas which cover the following superficial muscles: m. gastrocnemius, caput mediales et caput laterales, m. peroneus longus, m. tibialis anterior, m. soleus. The electrical surface activity, collected in these areas for some segmented movements (dorsal and plantar flexions with and without load) was integrated and quantified. The individual and inter-individual variability in electrical activity was obtained from six subjects and discussed. The typical electromyography of the leg was established for the four segmental movements investigated. This analysis had also lead to determine the most suitable electrode site for each of the superficial muscles. This study confirms the functional role classically attributed to these various muscles.

Adolescent↗
PubMed1978

Ionic currents in mammalian fast skeletal muscle.

1. The double sucrose-gap technique has been applied to rat skeletal muscle fibres to study the ionic currents under voltage-clamp conditions. 2. The iliacus muscle was found to be of 'fast' type according to the characteristics of the twitch generated by an action potential. 3. Micro-electrode measurements have shown that the intracellular potential is under good control even when an inward current develops. 4. The components of an equivalent circuit with two time constants have been estimated from the records of the capacitive current. 5. In rat muscle, between 15 and 21 degrees C, inward and outward currents are similar to sodium and potassium currents found in frog muscle at lower temperature (1--3 degrees C). 6. The inward current which depends on [Na]o and is abolished by tetrodotoxin is carried by sodium ions. Related to the mean value for the holding potential (-90.5 mV) this current reaches its maximum amplitude a +40 and +50 mV, reverses between +130 and +150 mV and its half inactivation occurs between +14 and +22 mV. The effect of low doses of tetrodotoxin suggests that two components participate in the sodium current. 7. The delayed outward current which shows inactivation is divided in two components: (i) the fast has a linear instantaneous current-voltage relation and differs from the fast component of frog muscle in that its equilibrium potential is more negative than the resting potential; (ii) the slow has a linear instantaneous current-voltage relation and the mean value for its equilibrium potential is 26 mV less negative than the resting potential. 8. Inward-going rectification is present in rat muscle.

Action Potentials↗
PubMed1978

[Acquired interventricular communications in bacterial endocarditis. Apropos of a case with review of the literature].

The case reported here concerns a female of 33 who presented, during the course of an acute bacterial aortitis which had been treated, with an inflammatory perforation of the membranous septum. The clinical picture consisted of an association of very severe heart failure with severe aortic incompetence, an apical pansystolic murmur, and atrioventricular conduction defects. Although it was carried out in the presence of active endocarditis (valve cultures positive for streptococci), operative intervention (Patch + Starr) allowed rapid healing and excellent cardiovascular function after a 30 month follow-up period. Careful study of this case and of the eleven others in the literature has enabled us to underline the following points:--the sudden appearance, in a case with infective aortic incompetence, of a gross pansystolic murmur associated with atrial or intraventricular conduction defects, should be taken as suggesting a septal perforation;--examination of the haemodynamic system in such a case runs certain risks, and should never be allowed to delay the operation, which must always be carried out urgently;--despite the unfavourable operative conditions, the results strongly support the need for surgical intervention in these patients in good time.

Adolescent↗
PubMed1976

Voltage clamp with double sucrose gap technique. External series resistance compensation.

In this paper we deal with the double sucrose-gap voltage clamp technique. To perform a reliable clamp or to analyze the intracellular potential distribution, any external series resistance in the artificial node must be taken into account for it induces an instability in the external potential as soon as a current develops. A circuit was designed to compensate for this error, it has been found effective on an analog model and on experimental uni- or multicellular preparations. The attenuation in series resistance frequently causes ringing in the step response. This behavior was studied theoretically and also simulated with analog models where a selective bridged-T network was found to represent the electrical characteristics of the preparation when associated with the chamber and control electronics. A residual series resistance was found and is considered to be a part of the preparation. Characteristics necessary to obtain best results are proposed, for a preparation to be studied in experiments utilizing the double sucrose gap technique with external series resistance compensation.

Cell Physiological Phenomena↗