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Biomedical subjects

H Meves

Publications and source records attributed to H Meves.

At least 37 records · Page 2Linked to original sources
PubMed1990

A slow component in the gating current of the frog node of Ranvier.

The slow component of the gating current on-response has been studied on voltage-clamped nodes of Ranvier of the frog Rana esculenta. At 0 mV and 20 degrees C the charge and the time constant of the slow component were on average 37.1 fC and 0.39 ms, respectively. The slow component could be abolished by shifting the holding potential from its usual value (-100 mV) to -60 mV. Repolarization to -100 mV for 2 ms was sufficient for complete recovery of the slow component. The local anaesthetic benzocaine (1 mM) reduced the fast component (measured at 0 mV) on average to 54% and the slow component (also measured at 0 mV) to 70% of the control value. In the potential range from -60 to 60 mV the charge of the slow component increased slightly with voltage. No significant voltage dependence of its time constant was observed. The slow component most likely reflects charge movement between different open states; it does not seem to be related to inactivation of the sodium channels or activation of the potassium channels.

Animals↗
PubMed1988

The action of arginine-specific reagents on ionic and gating currents in frog myelinated nerve.

(1) The effect of arginine-specific reagents on the sodium current (INa), potassium current (IK) and gating current (Igat) of myelinated nerve fibres was investigated. (2) Externally applied camphorquinone-10-sulfonic acid (Cqs-OH) had little effect, but 50 mM Cqs-OH applied to the cut ends of the fibre progressively reduced the amplitude of INa without significantly altering its time course. After 30 min INa was reduced to 52% (pH 9.0) or 66% (pH 6.75-7.6) of the control value. IK was decreased to a similar extent without changing its kinetics. Igat was less affected than the ionic currents. (3) Externally applied phenylglyoxal markedly reduced INa and Igat, but many fibres were lost during or shortly after the treatment. A few min treatment with 5 mM phenylglyoxal at pH 9 reduced INa to 20% and the on-response of Igat to 69.5%. The effect was to a large extent irreversible. (4) External nitrophenylglyoxal and hydroxyphenylglyoxal significantly reduced INa and were less damaging than phenylglyoxal. INa was decreased to 34.5% by 10 mM nitrophenylglyoxal and to 28.3% by 20 mM hydroxyphenylglyoxal. The effect of nitrophenylglyoxal was little reversible, but that of hydroxyphenylglyoxal to a large extent reversible. 20 mM hydroxyphenylglyoxal reduced the on-response of Igat to 62.5% of the control value, i.e. much less than INa. (5) 5 mM phenylglyoxal, 10 mM nitrophenylglyoxal and 20 mM hydroxyphenylglyoxal shifted the steady-state inactivation curve by 10-15 mV to more negative values of membrane potential but did not affect the descending branch of the INa(E) curve. (6) 20-30 mM glyoxal, 20 mM 1,2-cyclohexanedione and 10 mM 4-hydroxy-3-nitrophenylglyoxal had no effect on INa. (7) The results are compatible with the idea that arginine residues are principal components of the sodium channel macromolecule.

Aldehydes↗
PubMed1987

Gating current experiments on frog nodes of Ranvier treated with Centruroides sculpturatus toxins or aconitine.

(1) Gating currents were recorded from frog nodes of Ranvier treated either with toxins III or IV from the venom of the scorpion Centruroides sculpturatus or with the alkaloid toxin aconitine. (2) Toxins III or IV from Centruroides sculpturatus (which drastically reduce the sodium permeability PNa and slightly shift its voltage dependence in the depolarizing direction) caused a small depolarizing shift of the relation between charge (Qon) and membrane potential (E) without affecting the maximum charge Qon max. (3) On nodes treated with toxins III or IV from Centruroides sculpturatus, a depolarizing conditioning pulse (which transiently shifts the descending branch of the INa(E) curve by up to 60 mV in the hyperpolarizing direction) shifted the midpoint potential (Emid) of the Qon(E) curve by -17 mV and slightly increased the slope of the curve; it also decreased Qon max markedly but had little effect on Qon measured with small depolarizing pulses. By contrast, massive treatment with aconitine (which irreversibly shifts sodium activation in the hyperpolarizing direction) irreversibly shifted the midpoint potential of the Qon(E) curve from -28.5 to -69 mV and significantly increased Qon and Qoff measured with small depolarizing pulses; concomitantly, the voltage dependence of the on time constant of the charge movement [tau on(E)] was shifted by -44 mV. (4) The sodium current INa was exponential both in nodes treated with toxins III or IV of Centruroides sculpturatus and subjected to a depolarizing conditioning pulse and in aconitine-treated nodes; in the latter, INa started after a delay of 30-40 microseconds. The time constant of the sodium current. tau on Na, was larger than the time constant of the charge movement, tau on Q; the ratio tau on Q/tau on Na was 0.61 and 0.73 in the experiments with Centruroides sculpturatus toxins and aconitine, respectively. (5) The off time constant of the sodium current (tau off Na) was slightly increased in nodes treated with Centruroides sculpturatus toxins and subjected to a depolarizing conditioning pulse, whereas it was markedly increased in aconitine-treated nodes. With the former treatment, the off time constant of the charge movement (tau off Q) was unaffected but with aconitine treatment it was considerably increased although it remained smaller than tau off Na. Consequently, the ratio tau off Q/tau off Na (which is greater than or equal to 1 in untreated nodes) became smaller than one, reaching values as low as 0.58 and 0.44 in the experiments with Centruroides sculpturatus toxins and aconitine, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Aconitine↗
PubMed1987

Effects of reagents modifying carboxyl groups on the gating current of the myelinated nerve fiber.

The effect of the carboxyl group activating reagent N-ethoxy-carbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) on the gating current of the frog node of Ranvier was investigated. A 10-min treatment with 2 mM EEDQ (in the presence or absence of 10 mM ethylenediamine) irreversibly reduced the slope of the on charge-voltage relation Qon(E), shifted its midpoint potential Emid in the positive direction and reduced the maximum charge Qon max measured with strong depolarizing pulses. In six experiments, 2 mM EEDQ + 10 mM ethylenediamine increased the factor k (a reciprocal measure of the slope of the Qon(E) curve) from 16 to 22 mV. In five experiments, 2 mM EEDQ alone increased k from 16 to 23 mV. In a single experiment, 5 mM EEDQ + 10 mM ethylene diamine increased k from 17 to 31 mV. The reduction in slope suggests that EEDQ decreases the valence of the gating particles or reduces the fraction of the membrane field that they traverse. In addition, EEDQ (which inhibits inactivation of the sodium current, see M. Rack and K.H. Woll, J. Membrane Biol. 82:41-48, 1984) caused a small increase of the off charge Qoff, and a marked increase of the Qoff/Qon ratio, i.e. inhibited charge immobilization. Since the effects of EEDQ occurred regardless of the presence or absence of ethylenediamine, they are probably due to crosslinking reactions. The effects of EEDQ were compared with those of the water-soluble carbodiimide EDC. Treatment with 10 or 50 mM EDC (plus 10 or 50 mM ethylenediamine) caused a smaller increase of k than treatment with 2 mM EEDQ but reduced Qon max by the same amount.

Animals↗
PubMed1986

Kinetics of sodium current and gating current in the frog node of Ranvier.

The experiments were done on voltage-clamped nodes of Ranvier of the frog. The aim was to study the kinetics of sodium current INa and gating current Igat over a large potential range (-92 to -12 mV) and to compare the time constants for the turning-on of INa or Igat with those for the turning-off measured at the same potential. Sodium tail currents were recorded at different postpulse potentials. Inactivation was inhibited by a few min treatment with 0.5 mM chloramine-T (Wang 1984). The sodium permeability was activated by a 0.4 ms pulse from holding potential (-92 mV) to about 0 mV. At the peak of INa the membrane was repolarized to postpulse potentials between -92 and -12 mV. At E greater than -60 mV the tail currents decayed with two time constants, tau 1 and tau 2, reflecting presumably the turning-off and the inactivation of the sodium permeability. The relation between tau 1 and postpulse potential was bellshaped with a maximum at -32 mV. The tail currents could also be fitted by the Hodgkin-Huxley equation with the sodium activation variable m raised to the second or third power. At E less than -50 mV tau m off was equal to 2 tau 1 or 3 tau 1, respectively, whereas at E greater than -25 mV tau m off was equal to tau 1. In addition, the time constant of the turning-on of sodium activation m (tau m on) was determined, assuming INa approximately m2 (with a small initial delay) or INa approximately m3 (without an initial delay). At -22 mV and -12 mV the ratio tau m off/tau m on was close to 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Effects of toxins VI and VII from the scorpion Centruroides sculpturatus on the Na currents of the frog node of Ranvier.

New toxins, VI and VII, were purified from the venom of the North American scorpion, Centruroides sculpturatus, and studied in the voltage-clamped frog node of Ranvier. These toxins reduced peak inward Na currents and caused a transient, depolarization-induced shift in the voltage dependence of Na activation. Their effects were indistinguishable from those of toxins I, III and IV, as previously described by Meves et al. (1982). Toxin VII, 0.2 microgram/ml, shifted the voltage dependence of steady-state inactivation (h infinity). In four fibers, the mean shift of the h infinity (E) curve was -17 mV, compared to a mean shift of -28 mV in the descending branch of the INa(E) curve. The h infinity (E) curve with toxin VII was monotonic and inactivation was incomplete at positive potentials. Decreasing the pH from 7.4 to 5.7 increased the shift in the voltage dependence of activation with toxin. The increase with toxin VI at pH 5.7 was reversible on returning to pH 7.4, but the increase with toxin VII was not. The lack of reversibility of the effect of pH with toxin VII was quantified in two ways: the mean value of INa (measured at -62 mV with a conditioning pulse) at pH 7.4 was 5.1 times larger after treatment than before treatment with 0.1 microgram/ml of toxin VII at pH 5.7; the average concentration of toxin VII required for a shift of -30 mV at pH 7.4 was decreased by a factor of 4.3, to 0.19 microgram/ml (26 nM), by pretreatment at pH 5.7.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Interactions of scorpion toxins with the sodium channel.

It is evident from the data reviewed that scorpion toxins can be distinguished on the basis of three properties: their effects on Na currents, their specific binding to excitable membranes, and the effects of depolarization and pH on binding and on effect. Additional work with other scorpion toxins is required to establish the degree of correlation between the three properties for each class of toxin. Further investigations with this family of homologous proteins will undoubtedly contribute not only to our understanding of the toxins themselves but also to our understanding of the structure and function of the Na channel.

Amino Acid Sequence↗
PubMed1986

Sodium current and gating current experiments on the node of Ranvier.

Sodium tail currents of the frog node of Ranvier were recorded at different postpulse potentials. Inactivation was inhibited with chloramine-T. At E greater than -60 mV the tail currents decayed with two time constants, tau 1 and tau 2, reflecting presumably the turning-off and the inactivation of the sodium permeability. In the potential range -42 to -12 mV tau 1 (thought to equal tau m off) was not significantly different from the time constant of the turning-on of sodium activation m, tau m on. Similarly, no significant difference between tau on and tau off of the gating current was found if both were measured at the same potential.

Animals↗
PubMed1984

Voltage-dependent effect of a scorpion toxin on sodium current inactivation.

In voltage clamped nodes of Ranvier inactivation of the sodium permeability is slowed by toxin V from the scorpion Centruroides sculpturatus, by sea anemone toxin ATX II or by internally applied KIO3. The slow decay of the Na inward current is markedly accelerated if the test pulse is preceded by a depolarizing conditioning pulse followed by a 10-500 ms pause. This phenomenon was studied in detail, using conditioning pulses of varying amplitude and up to 15 s duration. In nodes treated with toxin V a 20 ms conditioning pulse to positive potentials was sufficient to produce a clear acceleration of the decay of the Na current and a reduction of the inward current remaining at the end of a 50 ms test pulse, i.e. a weakening of the toxin effect. In nodes treated with ATX II or internal KIO3 longer conditioning pulses were required. A similar effect of conditioning pulses on the decaying phase of the Na current was also observed in untreated fibres. To study the phenomenon quantitatively we fitted the decaying phase of the inward Na current with the equation INa = A exp(-t/tau 1) + B exp(-t/tau 2) + C. The effect of depolarizing conditioning pulses could be described as an increase of A, a decrease of B and C and a reduction of the time constants tau 1 and tau 2. I50/Ipeak, the normalised inward current remaining at the end of a 50 ms test pulse, decreased exponentially with increasing duration of the conditioning pulse to a steady-state value. The time constant tau and the steady-state value depended on the potential during the conditioning pulse. For nodes treated with toxin V, tau was 0.24 s at 0 mV and 12 degrees C and half inhibition occurred at -42 mV. The time constant tau was larger for nodes treated with ATX II or internal KIO3. At positive potentials, I50 was reduced to 20% of the control value in toxin V-treated nodes, but only to 70% in KIO3-treated nodes. Recovery from the effect of the conditioning pulse was studied by varying the pause between conditioning pulse and test pulse; recovery was 66-100% complete after 500 ms. The results are interpreted by assuming that a depolarizing conditioning pulse (a) accelerates inactivation of the sodium permeability and (b) causes dissociation of the toxin-receptor complex or transition into an inactive state. The latter effect occurs in toxin V-treated fibres but not in those treated with ATX II or KIO3.

Animals↗
PubMed1984

Biochemical and electrophysiological characteristics of toxins isolated from the venom of the scorpion Centruroides sculpturatus.

Recent progress in biochemical, structural and physiological studies has revealed several interesting properties of the toxins from the American scorpion, Centruroides sculpturatus. These toxins, together with similar toxins from other species of scorpions, comprise a unique family of homologous proteins with phylogenetically related structural differences. There is now evidence from both binding and electrophysiological studies that two distinct classes of toxins are present in the venom of C. sculpturatus. One class of toxins markedly slows inactivation of the sodium permeability but has no demonstrable effect on activation, whereas the second class induces a transient shift in the voltage-dependence of activation. Both groups make inactivation incomplete.

Amino Acid Sequence↗
PubMed1983

Preparation and properties of fluorescence labeled neuro- and cardiotoxin II from the sea anemone (Anemonia sulcata).

Labeling of the sea anemone toxin II with fluoresceinisothiocyanate is described. The native toxin and low molecular weight fluorescent compounds were completely separated from the derivative. Compared to fluorescein, the fluorescence of the toxin-derivative has a red shift and a decreased quantum yield. Like the native toxin, the fluorescent derivative affects the voltage-dependent sodium channel in nerve membranes. Under voltage-clamp conditions, the effect of the modified toxin on the inactivation of sodium channels was 45% of that of the unlabeled toxin.

Action Potentials↗
PubMed1982

Effect of toxins isolated from the venom of the scorpion Centruroides sculpturatus on the Na currents of the node of Ranvier.

1. The effect of various toxin fractions isolated by Watt et al. (1978) from the venom of the scorpion Centruroides sculpturatus Ewing on the Na currents of the node of Ranvier has been studied with the voltage clamp method. 2. The toxin fractions were applied externally. The most potent fractions were toxins III, IV and V which were effective in concentrations of 0.33-3.33 microgram/ml. The effect of toxins III and IV was quite different from that of toxin V. 3. In toxin III or IV - treated nodes a strong depolarizing pulse was followed by a transient shift of the negative resistance branch of the INa (E) curve to more negative potentials. The amount of shift varied between -10 and -60 mV. A 500 ms depolarizing pulse of small amplitude produced a slowly developing Na inward current which slowly decayed after the end of the pulse. Inactivation was incomplete, even with 500 ms pulses to 0 mV. 4. The transient shift of the INa (E) curve was not seen in nodes treated with toxin V. This toxin merely caused slow and incomplete Na inactivation. The effect of toxin IV was not suppressed by a four times higher concentration of toxin V, suggesting that the two toxins act on different receptors. 5. Toxin I acted like toxin IV but was about 10 times less potent. The effect of high concentrations of variants 1, 2, 3, 5, 6 resembled tha of toxin V. 6. All effects observed with toxin III or IV were also seen with the whole venom (cf. Cahalan 1975).

Animals↗
PubMed1981

The effect of external potassium on the removal of sodium inactivation in squid giant axons.

1. The effect of external and internal electrolytes on the parameters of the Na conductance, in particular on the time constant of removal of Na inactivation, was studied in intact and perfused squid giant axons under voltage-clamp conditions. 2. Adding 20-40 mM-KCl, -CsCl or -RbCl to K-free sea water reversibly increased the time constant of removal of inactivation by a factor of about 1.3; adding 20 mM-NaCl had no effect. The time constant of development of inactivation was decreased. The results are consistent with a -5 mV shift of the tau h(V) curve. The sodium activation (m infinity 3) and inactivation (h infinity) curves were shifted by the same amount. 3. Raising external Ca, by contrast, decreased the time constant of removal of inactivation and increased the time constant of development of inactivation, i.e. shifted the tau h(V) curve to more positive internal potentials. A free Ca concentration of 0.1 mM in the internal solution had no effect on Na inactivation. 3. The observations are compatible with the idea that external K, Cs or Rb interfere with the binding of Ca to negative fixed charges at the outer side of the membrane, thereby causing a shift in the opposite direction to the shift produced by raising external Ca. 5. Replacing two thirds of the internal K by Na reversibly increased the time constant of removal of sodium inactivation and moved the tau h(V) curve in the vertical direction.

Animals↗
PubMed1981

Inactivation of the Na permeability in squid giant axons.

Inactivation of the Na permeability has been studied in intact and perfused squid giant axons with the voltage clamp method. The main results are: 1. Upon depolarization inactivation develops along an exponential time course; the upper limit for an initial delay in the development of inactivation is 50-100 musec. 2. Adding 20-40 mM KCl to K-free external solution accelerates the development of inactivation and slows its removal. 3. Scorpion venoms increase the maintained conductance, i.e. make inactivation less complete; the voltage dependence of the maintained conductance is different from that of the peak conductance.

Action Potentials↗
PubMed1980

The time course of sodium inactivation in squid giant axons.

1. The time course of Na inactivation was studied in intact and perfused squid giant axons under voltage-clamp conditions. 2. The pulse programme consisted of a conditioning pulse of varying duration, followed after an interval of 3-8 msec by test pulse. The measurements were done in sea water with 1/3 or 1/5 of the normal Na concentration. In most experiments a 100 microseconds conditioning pulse was sufficient to reduce INa peak elicited by the test pulse. In some experiments even a 50 microseconds conditioning pulse produced a clear reversible decrease of INa peak. We conclude that the upper limit for an initial delay in the development of inactivation is 50-100 microseconds; this applies to temperatures between 0 and 13 degrees C and membrane potentials between -40 and 15 mV. The decrease of INa peak with increasing duration of the conditioning pulse was consistent with an exponential decay starting at 50 or 100 microseconds. 3. With large Na currents in full Na sea water the time course of inactivation became sigmoid. This is attributed to a long-lasting tail of inward current which follows the conditioning pulse and produces a voltage drop across the series resistance. 4. If the conditioning pulse and the test pulse were not separated by an interval, INa peak showed a sigmoid dependence on the duration of the conditioning pulse. This phenomenon is predicted by the equations of Hodgkin & Huxley (1952) as first pointed out by Kniffki, Siemen & Vogel (1978). With sufficiently strong conditioning pulses INa peak could even increase in size.

Animals↗