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Biomedical subjects

D Siemen

Publications and source records attributed to D Siemen.

23 records · Page 2Linked to original sources
PubMed1986

Slow permeation of organic cations in acetylcholine receptor channels.

Block, permeation, and agonist action of small organic amine compounds were studied in acetylcholine receptor (AChR) channels. Single channel conductances were calculated from fluctuation analysis at the frog neuromuscular junction and measured by patch clamp of cultured rat myotubes. The conductance was depressed by a few millimolar external dimethylammonium, arginine, dimethyldiethanolammonium, and Tris. Except with dimethylammonium, the block was intensified with hyperpolarization. A two-barrier Eyring model describes the slowed permeation and voltage dependence well for the three less permeant test cations. The cations were assumed to pause at a site halfway across the electric field of the channel while passing through it. For the voltage-independent action of highly permeant dimethylammonium, a more appropriate model might be a superficial binding site that did not prevent the flow of other ions, but depressed it. Solutions of several amine compounds were found to have agonist activity at millimolar concentrations, inducing brief openings of AChR channels on rat myotubes in the absence of ACh.

Animals↗
PubMed1985

Electrophysiological and neurobiochemical evidence for the blockade of a potassium channel by dendrotoxin.

The effects of dendrotoxin (DTX), a toxic peptide from Dendroaspis angusticeps venom, were studied electrophysiologically on peripheral frog nerve fibres, and biochemically on large synaptosomes from rat brain. On nerve fibres, DTX reduced the amplitude and prolonged the duration of the action potential; even at 0.1 nmol/l DTX produced significant effects. Maximum block of potassium currents occurred at about 30 nmol/l. Turning on of the remaining current was slowed. Reversibility was incomplete. The reduction of potassium currents was between 31% and 85% at 85 nmol/l DTX (n = 8). The remainder appeared to be resistant to DTX. Sodium channels were not affected. On large synaptosomes DTX (above 1 nmol/l) produced a slight depolarization, indicated by an outward shift of the lipophilic cation tetraphenylphosphonium, and promoted the release of radioactivity after preloading with [3H] GABA. DTX had similar potency but lower efficacy in this respect than sea anemone toxin II (ATX II). In contrast to the effects of ATX II, those due to DTX were only partially inhibited by tetrodotoxin. The actions of 4-aminopyridine resembled those of DTX, but the latter was about 500 times more potent. The electrophysiological data provide direct evidence for blockade of a potassium channel by DTX. This action is sufficient to explain the biochemical observations, although additional effects on synaptosomes cannot be excluded.

Action Potentials↗
PubMed1981

Development of sodium permeability inactivation in nodal membranes.

1. The time course of inactivation of the sodium permeability was studied in myelinated nerve fibres of Xenopus laevis using the voltage-clamp technique of Nonner (1969). The potassium currents were blocked by 10 mM-tetraethylammonium chloride (TEA). The remaining currents were corrected for leakage and capacity currents. 2. The decay of the sodium current was double-exponential confirming Chiu's (1977) findings The slower time constant was observed in TEA-free solutions by clamping to VK in high potassium concentrations. 3. The fast time constant was similar to tau h of Frankenhaeuser (1960), whereas the slower time constant was about four times larger and also decreased with increasing depolarization. 4. Arrhenius plots of both time constants can be well approximated by straight lines for temperatures between 0 and 25 degrees C. 5. The entire sodium current induced by single voltage-clamp pulses was fitted by a non-linear least-square routine to the Frankenhaeuser-Huxley equations extended by Chiu's three-state kinetics. With rare exceptions for potentials between 37 and 70 mV the fit was better without a delay in the onset of the inactivation of the sodium current. 6. The time course of inactivation was also studied in two-pulse experiments where a prepulse of varying duration was directly followed by a test pulse. The peak sodium currents were normalized by the associated peak currents without a prepulse. 7. The relative peak sodium current as a function of the prepulse duration had a sigmoid time course. The early deviation from an exponential decay is due to the activation arising during the prepulse and is implicit in the classical equations quoted above. It is therefore not necessarily a sign of a delay in the inactivation process. 8. To eliminate errors due to activation in two-pulse experiments, the decaying part of the test sodium currents was extrapolated back to the onset of the test pulse. These current values at t = 0 plotted as a function of the prepulse duration revealed no delay at the beginning of inactivation. Within the accuracy of our measurements a possible delay of more than 100 microseconds (at 5-10 degrees C) could be excluded.

Animals↗