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Biomedical subjects

W Ulbricht

Publications and source records attributed to W Ulbricht.

At least 19 recordsLinked to original sources
PubMed1991

Influence of Na+ and Li+ ions on the kinetics of sodium channel block by tetrodotoxin and saxitoxin.

Voltage clamp experiments were done on single myelinated frog nerve fibres. The rate of block of Na+ channels by tetrodotoxin (TTX) was obtained from changes in peak Na+ current during 1-Hz trains of depolarizing impulses. In hypertonic Na(+)-rich solution (216 mM) the stationary block was reduced compared with Na(+)-poor solutions (54 mM or less; tetramethylammonium ions substituting for Na+). Washout in 216 mM Na+ was faster than in 54 mM Na+. Concentration of Na+ [( Na+]) little affected onset of block. After equilibration in Na(+)-poor TTX solution, a sudden application of Na(+)-rich toxin solution led to a partial relief from block that proceeded faster than the onset in the latter solution. Comparable results were obtained with saxitoxin (STX) and in analogous Li+ solutions. Most of the observed phenomena could be quantitatively fitted by a cyclic model in which cations favour the transition of channels (unblocked and blocked) from a high- to a low-affinity state from which toxin dissociates faster.

Animals↗
PubMed1991

Chloramine-T effect on sodium conductance of neuroblastoma cells as studied by whole-cell clamp and single-channel analysis.

Patch-clamp experiments were done on sodium channels of neuroblastoma cells (N1E-115) in the presence of tetraethylammonium ions to block potassium channels. In Ringer solution whole-cell records revealed a diphasic INa inactivation with the fast (tau 0) component. being clearly larger than the slow (tau 1 approximately 3 tau 0) component. In single-channel studies on inside-out patches the mean open time, to, turned out to be only a fraction of tau 0 and almost independent of membrane potential. After external application of chloramine-T INa inactivation of whole cells was delayed with both tau 0 and tau 1 increased, and incomplete, i.e. a persistent current component emerged. The latter was maximal at a more positive membrane potential than the peak current. Also, after chloramine-T treatment the peak INa increased, particularly at weak depolarizations. In inside-out patches the equally effective internal application of chloramine-T led to bursting channel openings with mean burst times (tb) approximately 6 ms, and gap times (tg) approximately 20 ms, where gap is defined as a closure of greater than or equal to 1.5 ms. Within the bursts to was approximately 2 ms, again clearly shorter than tau 0; the mean close time, tc was approximately 0.5 ms. The single-channel conductance was approximately 13 pS and unaffected by chloramine-T. Diphasic INa inactivation and the fact that to less than tau 0 led to an extension of the model of Aldrich and Stevens [J Neurosci 7:418-431 (1987)], in which overall kinetics is determined by the openings rather than closures of the sodium channels.(ABSTRACT TRUNCATED AT 250 WORDS)

Chloramines↗
PubMed1990

The inactivation of sodium channels in the node of Ranvier and its chemical modification.

The many experimental studies reported demonstrate the complexity of what is termed inactivation, the decrease of current flow through sodium channels at maintained depolarization. Even at the normal resting potential of, say, -70 mV for a frog node of Ranvier, ca. 20% of the channels are closed and inactivated, i.e., incapable of passing current on a sudden depolarization, in contrast to the remaining 80% of closed but resting channels. The term inactivation has thus evolved from bulk current ("macroscopic") phenomena and is applied to channels although its single-channel ("microscopic") basis is not entirely clear and may even vary among preparations. It is conceivable that the macroscopic phenomenon may have more than a single microscopic cause; this point will probably not be settled until a physical description of the conformational states of the channel macromolecule becomes available. At any rate, channel transition into an inactivated closed state can be easily affected by numerous reagents of highly diverse chemical nature and, most likely, different primary sites of action as already suggested by the sidedness of effective application, e.g., iodate and endopeptidases to the inside, polypeptide toxins to the outside. But also the search for a common denominator, a secondary target of all these treatments, has not been very successful as demonstrated by the experiments with group-specific reagents. Since modification of inactivation is often accompanied by shifts in the voltage dependence of gating parameters, a target could be the "voltage sensor" of the channel, charged and/or dipolar components of the channel macromolecule that, by being moved in the electric field, somehow induce gating and whose movement is measured as gating current (e.g, Hille, 1984). The fraction of open channels as a function of membrane potential, F(E), may serve as an indicator. It may be simply shifted (to more negative potentials) as by veratridine (Leibowitz et al., 1987) or flattened (reduction of gating charge?) and shifted (in the positive direction) as by Anemonia sulcata toxin II (Ulbricht and Schmidtmayer, 1981) or chloramine-T (Drews, 1987). On the other hand, the steady-state inactivation curve is shifted to more negative potentials by the toxin (Ulbricht and Schmidtmayer, 1981), but to more positive potentials by chloramine-T (Wang, 1984a; Schmidtmayer, 1985). Obviously, modifiers may affect activation and inactivation quite differently, a result that touches on the question as to what extent inactivation derives its potential dependence from activation.(ABSTRACT TRUNCATED AT 400 WORDS)

Alkaloids↗
PubMed1987

[Adipocyte volume and count in obesity during weight reduction].

In the subcutaneous fatty tissue of 27 adipose patients the number and volume of adipocytes were determined before and after a stationary weight reduction. 47 normal test persons served as comparison. Under stationary weight reduction the volume of adipocytes significantly decreased, whereas the number of adipocytes remained constant. The subdivision of the obesity according to the cellularity of the fatty tissue into a hypertrophic and a hypertrophic hypercellular form is proposed. A possible indication for the determination of the volume of fat cells in adipose patients is given.

Adipose Tissue↗
PubMed1987

Action of benzocaine on sodium channels of frog nodes of Ranvier treated with chloramine-T.

Single myelinated nerve fibres of the frog Rana esculenta were voltage clamped in solutions containing 10 mM TEA to block potassium channels. Reduction of peak INa was measured after equilibrating the membrane in solution containing benzocaine between 0.025 and 2.0 mM. A Hill plot of this effect revealed a slope nH approximately 1 between 0.25 and 1.0 mM but showed deviations for the lowest concentrations (nH less than 1) and the highest concentration (nH greater than 1). Treatment with 0.6 mM chloramine-T irreversibly partially inhibited inactivation of sodium channels leading to a large INa component persisting during depolarization. After treatment the benzocaine effect on peak INa (tested with 0.25-1.0 mM) was unchanged but the persistent component was much more depressed. Benzocaine shifted the steady-state inactivation curve to more negative potentials. This was also observed after chloramine-T treatment which itself produced a curve of decreased slope, shifted to more positive potentials. Recovery from inactivation was studied at different levels of hyperpolarization; it was diphasic in anaesthetic-free solutions before and after chloramine-T treatment although slowed in the latter case. In benzocaine recovery started with a delay (less than 0.6 ms at 16-18 degrees C) and proceeded with a single time constant that decreased with increasing hyperpolarization, was independent of benzocaine concentration and not affected by chloramine-T. The results are compatible with the idea that the affinity of the binding site for benzocaine increases when the channel state changes from resting to open to inactivated with equilibrium dissociation constants of the reaction with resting channels, KR = 0.7 mM and with inactivated channels, KI = 0.04 mM.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Distinctly different rates of benzocaine action on sodium channels of Ranvier nodes kept open by chloramine-T and veratridine.

Single myelinated nerve fibres of the frog, Rana esculenta, were voltage clamped in a fast-exchange chamber in the presence of 10 mM TEA to block potassium channels. After treatment with 0.6 mM chloramine-T for 1-4 min a sizeable INa component persisted even during a 14-s depolarizing impulse. Changing the perfusate to Ringer solution + 1 mM benzocaine resulted in a fast reduction (half time ca. 0.06 s) of the persistent INa, comparable to the rate of block of peak INa during a series of short impulses before chloramine-T. In the presence of 60 microM veratridine the peak INa was followed by a slow exponential (tau s) reincrease of inward current, Is, that did not appreciably inactivate. Application of 0.25 mM benzocaine during a 14-s depolarizing impulse caused Is to decrease exponentially with a large time constant, tau on of 4.3 s. Recovery on washout proceeded with tau off = 3.4s. Tau on was little dependent on benzocaine concentration and was 4.5 s on the average in 1 mM. Tau on in 25 microM was insignificantly (15%) larger than in 1 mM if tested on the same fibre. After equilibration in 25 microM, 0.25 mM and 1 microM, Is(t = 14s) was reduced to 0.69, 0.30, and 0.10, respectively, of the value without anaesthetic. Cooling by only 4-5 degrees C reduced Is and much increased tau s. tau on (1 mM benzocaine) increased almost in proportion to tau s. Tail currents during a series of pulses (1.1 s every 2.5 s) were reduced by 0.25 mM benzocaine clearly faster (tau on = 1.3 s) than Is during a long pulse of the same amplitude.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Combined action of intraaxonal iodate and external sea anemone toxin ATX II on sodium channel inactivation of frog nerve fibres.

Voltage clamp experiments were done on single myelinated nerve fibres of the frog, Rana esculenta, with 10 mM TEA+ in the external solutions to block potassium channels. Iodate (20, 40 or 100 mM KIO3) was applied to the axoplasmic side of the nodal membrane by diffusion from a cut internode. The effect of 20 mM started within a few minutes and reached a stationary value after ca. 20 min which was maintained for another 15 min. The size of the effect was independent of the iodate concentrations tested. Iodate action could not be reversed even after only a 2-min application. When the effect was fully established, iodate increased the faster time constant of inactivation ca. 1.2 times, the slower one ca. 1.7 times. Iodate also induced a persistent (for seconds) INa component that was, at the end of a 15-ms pulse (I15ms), 6% of the early peak INa of the control. Experiments with conditioning prepulses revealed a non-monotonic h infinity -V curve in iodate with finite h infinity values throughout. Increasing [Ca2+]0 from 2 to 10 mM shifted peak INa (V) and I15ms (V) by 10-15 mV to more positive potentials. In contrast, as shown in previous experiments, I15ms induced by sea anemone toxin ATX II was nearly abolished (h infinity approximately equal to 0) for 60 less than V less than 80 mV on increasing [Ca2+]0.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1982

Rate of action of Anemonia sulcata toxin II on sodium channels in myelinated nerve fibres.

1. The effect of Anemonia sulcata toxin II (ATX II) on single myelinated nerve fibres of the frog, Rana esculenta, was investigated. 2. ATX II promptly and reversibly increased the duration of action potentials; on applying 9.5 micro M the time, t0.5, to reach half of the final effect was 2.6 s. In the presence of 10 mM tetraethylammonium the duration was very sensitive to ATX II and as little as 10 nM could be detected. 3. The underlying mechanism was a diphasic incomplete inactivation of sodium channels which, at 15 degrees C, caused a sizeable INa to persist after 15 ms depolarization (I15ms). 4. On applying 5 micro M (1.25 micro M) ATX II at ca. 15 degrees C, I15ms developed with a sigmoid time course whose t0.5 was 1.5 s (2.6 s) and on washing declined in a near-exponential fashion with tau off = 6.1 s (6.4 s). Washing after a short (1-2s) application led to a transient considerable increase in I15ms followed by a faster decline with tau'off less than tau off. 5. Cooling decreased the rate of action with a Q10 of 1/tau0.5 = 1.9 and of 1/tau off = 2.0 (between 7 and 14 degrees C). ATX I (up to 15 micro M) was ineffective and did not antagonize ATX II. 6. Both rates of diffusional access and reaction seem to contribute to the rate of action. The results suggest a superficial binding site.

Animals↗
PubMed1982

[Migraine accompagnée].

The symptomatology of migraine accompagnée is described. The order of the symptoms, the suspected localisation and the possibility of permanent defects, heredity and treatment are discussed. The results obtained by traditional methods of examination such as blood flow measurements, arteriography and EEG are presented, as are those of more modern techniques such as skull rheography and computed tomography.

Aphasia↗
PubMed1981

Modification of sodium channels in myelinated nerve by Anemonia sulcata toxin II.

1. Single myelinated nerve fibres of the frog, Rana esculenta, were investigated predominantly in voltage clamp experiments. 2. Sodium current (INa) inactivation was measured in the presence of 10 mM TEA to suppress IK. Inactivation was diphasic but complete in toxin-free solution; it was delayed and became incomplete in Anemonia sulcata toxin II (ATX II) leading to persistent INa flow even during long depolarizations. The effects were reversible. Activation was not affected. 3. The persistent INa component increased with increasing toxin concentration and saturated at ca. 15 microM. The lowest concentration yielding unequivocal effects in the voltage clamp was 0.5 microM. 4. The curve relating the steady-state inactivation parameter, h infinity to the conditioning potential V became non-monotonic in ATX II i.e. dh infinity/dV greater than 0 for V greater than 30 mV. 5. Inactivation could be formally described by a three-state model with two conducting (h2 and h2) and one closed state (x) in the sequence h1 in equilibrium x in equilibrium h2. 6. Ca2+ modifies h2(V) more than h1(V) whose reaction to Ca2+ is similar to h(V) in toxin-free solution. The Ca2+ effect is very rapid and reversible.

Animals↗
PubMed1980

Interaction of lidocaine and benzocaine in blocking sodium channels.

1. Single myelinated nerve fibres of the frog, Rana esculenta, were investigated in voltage and current clamp experiments at pH 7.2 2. Measured with infrequent test pulses, 0.123 mM lidocaine reduced INa to 54%, 0.25 mM benzocaine to 40% and the mixture 0.125 mM lidocaine +/- 0.25 mM benzocaine to 31% of the control. When hyperpolarizing prepulses (V = -40 mV for 15 ms) preceded the test pulses the respective reductions were to 58%, 74% and 55% i.e. adding benzocaine to lidocaine had little additional effect. 3. Increasing the rate of the prepulse-test pulse pairs from 1 to 20 Hz did not change INa in benzocaine but gradually relieved block by lidocaine; in the mixture this change was much reduced or absent. 4. Switching off prepulses (at 20 Hz) led to a gradual decrease of INa in lidocaine but to a prompt fall in benzocaine and in the mixture. 5. 0.25 mM lidocaine and 0.5 mM benzocaine were approximately equieffective in reducing INa (no prepulse) to 29% and 24%; a one-to-one mixture of the two solutions (0.125 mM lidocaine + 0.25 mM benzocaine) reduced to 27%. 6. In current clamp experiments 0.25 mM lidocaine and 0.36 mM benzocaine reduced the maximum rate of rise of the action potential to 32% and 30%, the mixture of solutions (0.125 mM lidocaine + 0.18 mM benzocaine) to 29%. 7. These results are fully compatible with the idea of a single common binding site for which lidocaine and benzocaine compete.

Animals↗
PubMed1978

Rates of block by procaine and benzocaine and the procaine-benzocaine interaction at the node of Ranvier.

1. Action potentials and their maximum rates of rise, VA, were measured in single myelinated nerve fibres of the frog, Rana esculenta at room temperature. 2. On applying 1 mM procaine (pH 7.2) at 20 Hz stimulus frequency, half of the final VA reduction was reached at ton = 0.27 s; on applying 0.5 mM benzocaine (pH 7,2) at 50 HZ, ton was 0.12 s. Increasing the stimulus frequency between 2 and 50 HZ increased the rate of block by procaine but not by benzocaine. 3. Recovery in Ringer solution (pH 7.2) from 30-s treatment with 1 mM procaine (pH 7.2), the equieffective 0.15 mM procaine (pH 8.9) and from 0.5 mM benzocaine (pH 7.2) was 54%, 31% and 70%, respectively, within 1 s. 4. Changing between alkaline Ringer solution (pH 8.9) and 1 mM procaine (pH 7.2) led to transitory excessive block. Changing between 1 mM procaine (pH 7.2) and acid Ringer solution (pH 6.0) and washing out 10 mM procaine (pH 5.5) with neutral Ringer solution also led to a non-monotonic change in VA. 5. If hyperpolarizing pulses (30 ms, 20 mV) preceded the stimuli, changing the frequency of the pulse pairs led to a gradual moderate relief of block in procaine, turning off prepulses (at 10 HZ) to a gradual increase of block. In benzocaine changing from 1 to 10 HZ had no effect but turning off prepulses led to a prompt large increase of block. In procaine + benzocaine the membrane responded much as in benzocaine alone. At 1 HZ (prepulses) VA in 0.4 mM procaine was smaller than in 0.4 mM procaine + 0.3 mM benzocaine. 6. These phenomena can be explained on the assumption of voltage-dependent binding of benzocaine and procaine to a common receptor. The rate of block appears to be limited by access to the receptor, more in the case of benzocaine than of procaine.

Action Potentials↗
PubMed1976

Block of potassium channels of the nodal membrane by 4-aminopyridine and its partial removal on depolarization.

1. Voltage clamp experiments were done on single myelinated nerve fibres of the frog, Rana esculenta. 2. 53 muM 4-aminopyridine (4-AP) reduced IK to about one-fifth if tested with infrequent (1/min) and short (10 ms) depolarizing pulses; the onset time constant under these circumstances was ca. 160 s (14-15 degrees C). After prolonged treatment the effect was virtually irreversible. 3. At equilibrium with 4-AP, increasing the frequency of short pulses removed part of the block, the block removal accelerating with increasing pulse duration and frequency. 4. In 53 muM 4-AP unblocking of K channels during long (0.8 s) depolarizing pulses proceeded with a time constant, taur, of ca. 0.2 s. Restoration of block at the resting potential proceeded with a much larger time constant, tau'r, of ca. 1 min. 5. The stationary fraction, rinfinity, of K channels conducting in 53 muM 4-AP was 0.66, 0.41, and 0.24 at V = 120, 50, and 0 mV, respectively. 6. In a series of experiments with [4-AP] varying between 13.3 and 848 muM, taur decreased from 0.25 to 0.10 s (V = 130 mV, ca. 17 degrees C) while rinfinity followed the empirical relation 1/rinfinity = 1 + ct + cv exp(-0.77 EF/RT) with E = V - 70 mV. ct and cv are dimensionless quantities that increase with [4-AP] and reflect the voltage-independent and voltage-dependent component, respectively, of block. 7. Block of K channels and partial removal are also observed with inward IK at raised [K+]O. Removal proceeds on depolarization even if IK is additionally but temporarily suppressed by tetraethylammonium. Hence neither direction nor amplitude of IK but only the pulse potential seems to determine the extent of block for a given [4-AP].

Animals↗