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G Ehrenstein

Publications and source records attributed to G Ehrenstein.

9 recordsLinked to original sources
PubMed1979

Comparison of ionic selectivity of batrachotoxin-activated channels with different tetrodotoxin dissociation constants.

The purpose of these experiments is to test whether the differences between normal and tetrodotoxin-resistant Na+ channels reside in the selectivity filter. To do this, we have compared the selectivity of batrachotoxin-activated channels for alkali cations, organic cations, and nonelectrolytes in two neuroblastoma clonal cell lines: N18, which has normal tetrodotoxin (TTX) sensitivity, and C9, which is relatively TTX-resistant. We have also studied the effect of H+ on Na+ permeability and on the interaction between TTX and its receptor site in both cell lines. There is no qualitative difference between the two cell lines in any of these properties. In both cell lines the batrachotoxin-activated Na+ channels have a selectivity sequence of Tl+ greater than Na+ greater than K+, guanidinium greater than Rb+ greater than Cs+, methylamine. Also, in both cell lines H+ blocks Na+ channels with a pKa of 5.5 and inhibits the action of TTX with the same pKa. These observations indicate that the selectivity filters of the Na+ channels in C9 and N18 do not differ significantly despite the 100-fold difference in TTX-affinity. Our selectivity studies of batrachotoxin-activated Na+ channels for both cell lines suggest that these toxin-activated Na+ channels have a limiting pore size of 3.8 x 6.0 A, as compared to a pore size of 3.0 x 5.0 A for potential-activated Na+ channels.

Animals↗
PubMed1978

Effects of yohimbine on squid axons.

Yohimbine, an indolealkylamine alkaloid, reduces the amplitude of the sodium current in the squid giant axon. For doses that reduce sodium current amplitude by up to 50%, there is no significant change in the kinetics or in any of the voltage-dependent parameters associated with sodium channels. The effective equilibrium constant for yohimbine binding to the sodium channel is 3 x 10(-4) M. Repetitive depolarizing pulses increase the inhibition of squid axon sodium current by yohimbine. This use-dependent inhibition is enhanced by increasing the concentration of yohimbine, by increasing the frequency of pulsing, and by increasing the magnitude or the duration of depolarization. It is reduced by hyperpolarizing prepulses. This behavior can be explained by a model wherein yohimbine binds more readily to open sodium channels than to closed sodium channels and wherein the Hodgkin-Huxley kinetic parameters are modified by the binding of the drug. This type of model may also explain the tonic and use-dependent inhibition previously described by others for local anesthetics.

Action Potentials↗
PubMed1978

Interaction between batrachotoxin and yohimbine.

The neurotoxins, batrachotoxin and veratridine, are specific activators of sodium channels and cause an increase in the rate of 22Na uptake in neuroblastoma cells. Yohimbine, an indolakylamine alkaloid, inhibits this batrachotoxin-induced 22Na uptake. The dose-response curve of yohimbine suggest that the inhibitor acts reversibly on a single class of binding sites with dissociation constant of 3--4 x 10(-5) M. The dissociation constant is not affected by depolarization from--41 to 0 mV. Kinetic and equilibrium experiments indicate that yohimbine is a competitive inhibitor of the action of batrachotoxin. These results support the conclusion that yohimbine inhibitis the sodium flux by acting on the channel gating mechanism rather than by occluding the channels.

Batrachotoxins↗
PubMed1978

Selectivity of cations and nonelectrolytes for acetylcholine-activated channels in cultured muscle cells.

The selectivity of acetylcholine (A-Ch)-activated channels for alkali cations, organic cations, and nonelectrolytes in cultured muscle cells has been studied. To test the effect of size, charge, and hydrogen-binding capacity of permeant molecules on their permeability, we have obtained the selectivity sequences of alkali cations, compared the permeability of pairs of permeant molecules with similar size and shape but differing in charge, and studied the permeability of amines of different hydrogen bonding capacity. ACh-activated channels transport alkali cations of small hydration radii and high mobility. The molecules with positive charge and (or) a hydrogen-bond donating moiety are more permeable than the ones without. On the other hand, several nonelectrolytes, i.e., ethylene glycol, formamide, and urea, do have a small, but measurable, permeability through the channels. These results are consistent with a model that ACh-activated channel is a water-filled pore containing dipoles or hydrogen bond accepting groups and a negative charged site with a pK of 4.8.

Animals↗
PubMed1975

The nature of the voltage-dependent conductance of the hemocyanin channel.

The electrical responses of individual hemocyanain channels in oxidized cholesterol membranes demonstrate that the voltage-dependent conductance of many-chanel membranes arises from two different mechanisms. These are the voltage-dependent redistribution of channels among several discrete single-channel conductance states themselves. The relaxation time for the discrete conductance changes is of the order of seconds nd the relaxation time of the continuous conductance changes is of the order 10(-4) seconds. As salt concentration in the bathing medium is increased, the single-channel conductance first increases lineary and then saturates. The characteristics of the saturation curves suggest that the continuous conductance changes occur at the edges of the channel and that the mean time an ion spends in the channel is 4 nanoseconds...

Cholesterol↗