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H H Wagner

Publications and source records attributed to H H Wagner.

At least 55 records · Page 3Linked to original sources
PubMed1975

The influence of pH on the rate of tetrodotoxin action on myelinated nerve fibres.

1. The experiments were done on single myelinated nerve fibres of Rana esculenta. The rates of toxin effect were studied either by measuring the maximum rate of rise, VA, of repetitively evoked action potentials or by measuring Na currents during periodic impulses in the voltage clamp. 2. VA measurements showed that in alkaline solutions (pH up to 8-8) the offset rate was unchanged while the onset was slowed in quantitative agreement with an assumed decrease in the active cationic form of tetrodotoxin. 3. Both VA measurements and those in the voltage clamp revealed a decrease in T'off, the offset time constant and in increase in the onset time constant, T'on, as the pH was lowered. 4. For tetrodotoxin concentrations, [TTX], up to 400 nM and pH values down to 5-3 the simple relation T'on/T'off = p'R held, where p'T is the constant factor by which the Na permeability was reduced at equilibrium with a given [TTX]. 5. The agreement between kinetic and equilibrium results was also valid when, at constant [TTX] and pH. p'T was modified by the holding potential during equilibration. 6. No unequivocal explanation of the results can be given but some of their features resemble acid catalysis.

Action Potentials↗
PubMed1973

The rate of action of tetrodotoxin on myelinated nerve fibres of Xenopus laevis and Rana esculenta.

1. The experiments were done on single Ranvier nodes of Xenopus laevis (voltage clamp) and Rana esculenta (action potentials). Rate and size of the effect of tetrodotoxin were determined by the reversible reduction of either the sodium inward current (Xenopus) or of V(A), the maximum rate of rise of the action potential (Rana).2. The results of tetrodotoxin block at equilibrium could be excellently fitted by assuming a one-to-one reaction between toxin molecules and sodium channels of the Xenopus membrane with an equilibrium dissociation constant K = 3.60 nM at room temperature. V(A) was not linearly related to the fraction of unblocked sodium channels and 10.9 nM tetrodotoxin was necessary on the average to reduce V(A) to 50% in Rana motor fibres; in sensory fibres a lower concentration sufficed.3. Onset and offset of the tetrodotoxin effect on Xenopus nodes could be quantitatively interpreted as being determined by the rates of the tetrodotoxin channel reaction. Experiments with 3.1 and 15.5 nM tetrodotoxin at room temperature yielded an association rate constant, k(1), of 2.94 x 10(6)M(-1) sec(-1) and a dissociation rate constant, k(2), of 1.42 x 10(-2) sec(-1). In these experiments the equilibrium dissociation constant, K, was 3.31 nM. If determined solely from the onset in the two tetrodotoxin concentrations, k(1) = 3.25 x 10(6)M(-1) sec(-1) and K = k(2)/k(1) = 4.08 nM was calculated.4. In Rana fibres the onset and offset of V(A) reduction by 15.5 and 31 nM tetrodotoxin was evaluated using the equilibrium effects of intermediary tetrodotoxin concentrations for calibration. The average results at room temperature were k(1) = 4 x 10(6)M(-1) sec(-1), k(2) = 1.4 x 10(-2) sec(-1) and K = 3.4 nM.5. The very short latency with which V(A) started to decline when tetrodotoxin was suddenly applied proved that the toxin had ready access to the membrane.6. The temperature dependence of k(1), k(2) and K in the Xenopus experiments could be described by Arrhenius plots yielding activation energies, E(a), of 9.8, 20.5 and 7.0 kcal/mole, respectively, corresponding to Q(10) values of 1.82, 3.42 and 1.53 (between 12 and 22 degrees C). For k(1), determined from onset alone, E(a) = 13.7 kcal/mole (Q(10) = 2.25) was obtained. Although in Rana the temperature dependence of the rate constants could not be determined directly, the Q(10) for k(2) must have been of the order of 3.7. The results suggest that the rate of the toxin action on the nodal membrane of Xenopus and Rana is limited by the tetrodotoxin-sodium site reaction.

Action Potentials↗