scholarly journals Charges and Potentials at the Nerve Surface

1968 ◽  
Vol 51 (2) ◽  
pp. 221-236 ◽  
Author(s):  
Bertil Hille
Keyword(s):  
Potassium Channels ◽  
Sodium Channels ◽  
Voltage Dependence ◽  
Divalent Cations ◽  
Fold Increase ◽  
Nerve Fibers ◽  
Hydrogen Ions ◽  
Acidic Group ◽  
Myelinated Nerve ◽  
Bathing Medium

The voltage dependence of the voltage clamp responses of myelinated nerve fibers depends on the concentration of divalent cations and of hydrogen ions in the bathing medium. In general, increases of the [Ca], [Ni], or [H] increase the depolarization needed to elicit a given response of the nerve. An e-fold increase of the [Ca] produces the following shifts of the voltage dependence of the parameters in the Hodgkin-Huxley model: m∞, 8.7 mv; h∞, 6.5 mv; τn, 0.0 mv. The same increase of the [H], if done below pH 5.5, produces the following shifts: m∞, 13.5 mv; h∞, 13.5 mv; τn, 13.5 mv; and if done above pH 5.5: m∞, 1.3 mv; h∞, 1.3 mv; τn, 4.0 mv. The voltage shifts are proportional to the logarithm of the concentration of the divalent ions and of the hydrogen ion. The observed voltage shifts are interpreted as evidence for negative fixed charges near the sodium and potassium channels. The charged groups are assumed to comprise several types, of varying affinity for divalent and hydrogen ions. The charges near the sodium channels differ from those near the potassium channels. As the pH is lowered below pH 6, the maximum sodium conductance decreases quickly and reversibly in a manner that suggests that the protonation of an acidic group with a pKa of 5.2 blocks individual sodium channels.

scholarly journals The Permeability of the Sodium Channel to Metal Cations in Myelinated Nerve

1972 ◽  
Vol 59 (6) ◽  
pp. 637-658 ◽  
Author(s):  
Bertil Hille
Keyword(s):  
Sodium Channels ◽  
Ionic Composition ◽  
Reversal Potential ◽  
Metal Cations ◽  
Ionic Currents ◽  
Giant Axon ◽  
Nerve Fibers ◽  
Myelinated Nerve ◽  
Bathing Medium ◽  
Goldman Equation

The relative permeability of sodium channels to eight metal cations is studied in myelinated nerve fibers. Ionic currents under voltage-clamp conditions are measured in Na-free solutions containing the test ion. Measured reversal potentials and the Goldman equation are used to calculate the permeability sequence: Na+ ≈ Li+ > Tl+ > K+. The ratio PK/PNa is 1/12. The permeabilities to Rb+, Cs+, Ca++, and Mg++ are too small to measure. The permeability ratios agree with observations on the squid giant axon and show that the reversal potential ENa differs significantly from the Nernst potential for Na+ in normal axons. Opening and closing rates for sodium channels are relatively insensitive to the ionic composition of the bathing medium, implying that gating is a structural property of the channel rather than a result of the movement or accumulation of particular ions around the channel. A previously proposed pore model of the channel accommodates the permeant metal cations in a partly hydrated form. The observed sequence of permeabilities follows the order expected for binding to a high field strength anion in Eisenman's theory of ion exchange equilibria.

scholarly journals The Inhibition of Sodium Currents in Myelinated Nerve by Quaternary Derivatives of Lidocaine

1973 ◽  
Vol 62 (1) ◽  
pp. 37-57 ◽  
Author(s):  
Gary R. Strichartz
Keyword(s):  
Sodium Channels ◽  
Voltage Dependence ◽  
Nerve Fibers ◽  
Sodium Currents ◽  
Myelinated Nerve ◽  
Variable Voltage ◽  
Electrical Gradient ◽  
A Site ◽  
Derivatives Of ◽  
Tonic Phase

The inhibition of sodium currents by quaternary derivatives of lidocaine was studied in single myelinated nerve fibers. Membrane currents were diminished little by external quaternary lidocaine (QX). QX present in the axoplasm (<0.5 mM) inhibited sodium currents by more than 90%. Inhibition occurred as the sum of a constant, tonic phase and a variable, voltage-sensitive phase. The voltage-sensitive inhibition was favored by the application of membrane potential patterns which produce large depolarizations when sodium channels are open. Voltage-sensitive inhibition could be reversed by small depolarizations which opened sodium channels. One explanation of this observation is that QX molecules enter open sodium channels from the axoplasmic side and bind within the channels. The voltage dependence of the inhibition by QX suggests that the drug binds at a site which is about halfway down the electrical gradient from inside to outside of the sodium channel.

scholarly journals Ionic Blockage of Sodium Channels in Nerve

1973 ◽  
Vol 61 (6) ◽  
pp. 687-708 ◽  
Author(s):  
Ann M. Woodhull
Keyword(s):  
Sodium Channel ◽  
Sodium Channels ◽  
Voltage Dependence ◽  
Hydrogen Ion ◽  
Ion Concentration ◽  
Hydrogen Ions ◽  
Sodium Permeability ◽  
Bathing Medium ◽  
Hydrogen Ion Concentration ◽  
Voltage Dependent

Increasing the hydrogen ion concentration of the bathing medium reversibly depresses the sodium permeability of voltage-clamped frog nerves. The depression depends on membrane voltage: changing from pH 7 to pH 5 causes a 60% reduction in sodium permeability at +20 mV, but only a 20% reduction at +180 mV. This voltage-dependent block of sodium channels by hydrogen ions is explained by assuming that hydrogen ions enter the open sodium channel and bind there, preventing sodium ion passage. The voltage dependence arises because the binding site is assumed to lie far enough across the membrane for bound ions to be affected by part of the potential difference across the membrane. Equations are derived for the general case where the blocking ion enters the channel from either side of the membrane. For H+ ion blockage, a simpler model, in which H+ enters the channel only from the bathing medium, is found to be sufficient. The dissociation constant of H+ ions from the channel site, 3.9 x 10-6 M (pKa 5.4), is like that of a carboxylic acid. From the voltage dependence of the block, this acid site is about one-quarter of the way across the membrane potential from the outside. In addition to blocking as described by the model, hydrogen ions also shift the responses of sodium channel "gates" to voltage, probably by altering the surface potential of the nerve. Evidence for voltage-dependent blockage by calcium ions is also presented.

scholarly journals The Inner Quaternary Ammonium Ion Receptor in Potassium Channels of the Node of Ranvier

1972 ◽  
Vol 59 (4) ◽  
pp. 388-400 ◽  
Author(s):  
Clay M. Armstrong ◽  
Bertil Hille
Keyword(s):  
Potassium Channels ◽  
Quaternary Ammonium ◽  
Node Of Ranvier ◽  
Nerve Fibers ◽  
Ammonium Ion ◽  
Ammonium Ions ◽  
Myelinated Nerve ◽  
Quaternary Ammonium Ions ◽  
Activation Gate ◽  
Almost All

Quaternary ammonium ions were applied to the inside of single myelinated nerve fibers by diffusion from a cut end. The resulting block of potassium channels in the node of Ranvier was studied under voltage-clamp conditions. The results agree in almost all respects with similar studies by Armstrong of squid giant axons. With tetraethylammonium ion (TEA), pentyltriethylammonium ion (C5), or nonyltriethylammonium ion (C9) inside the node, potassium current during a depolarization begins to rise at the normal rate, reaches a peak, and then falls again. This unusual inactivation is more complete with C9 than with TEA. Larger depolarizations give more block. Thus the block of potassium channels grows with time and voltage during a depolarization. The block reverses with repolarization, but for C9 full reversal takes seconds at -75 mv. The reversal is faster in 120 mM KCl Ringer's and slower during a hyperpolarization to -125 mv. All of these effects contrast with the time and voltage-independent block of potassium, channels seen with external quaternary ammonium ions on the node of Ranvier. External TEA, C5, and C9 block without inactivation. The external quaternary ammonium ion receptor appears to be distinct from the inner one. Apparently the inner quaternary ammonium ion receptor can be reached only when the activation gate for potassium channels is open. We suggest that the inner receptor lies within the channel and that the channel is a pore with its activation gate near the axoplasmic end.

scholarly journals Pharmacological Modifications of the Sodium Channels of Frog Nerve

1968 ◽  
Vol 51 (2) ◽  
pp. 199-219 ◽  
Author(s):  
Bertil Hille
Keyword(s):  
Sodium Channels ◽  
Nerve Fibers ◽  
Myelinated Nerve ◽  
Apparent Dissociation Constant ◽  
Specific Change ◽  
Myelinated Nerve Fibers ◽  
Sodium Activation ◽  
Sodium Inactivation ◽  
Na Ions ◽  
Ionic Forms

Voltage clamp measurements on myelinated nerve fibers show that tetrodotoxin, saxitoxin, and DDT specifically affect the sodium channels of the membrane. Tetrodotoxin and saxitoxin render the sodium channels impermeable to Na ions and to Li ions and probably prevent the opening of individual sodium channels when one toxin molecule binds to a channel. The apparent dissociation constant of the inhibitory complex is about 1 nM for the cationic forms of both toxins. The zwitter ionic forms are much less potent. On the other hand, DDT causes a fraction of the sodium channels that open during a depolarization to remain open for a longer time than is normal. The effect cannot be described as a specific change in sodium inactivation or as a specific change in sodium activation, for both processes continue to govern the opening of the sodium channels and neither process is able to close the channels. The effects of DDT are very similar to those of veratrine.

Dedifferentiation of the Axolemma Associated with Demyelination

1981 ◽  
Vol 39 ◽  
pp. 496-497 ◽  
Author(s):  
J. Rosenbluth ◽  
A. Sumner ◽  
T. Saida
Keyword(s):  
Sodium Channels ◽  
Peripheral Nerves ◽  
Freeze Fracture ◽  
Fracture Analysis ◽  
Nerve Fibers ◽  
High Concentration ◽  
Myelinated Nerve ◽  
Spinal Roots ◽  
Myelin Deficient

Freeze-fracture analysis of myelinated nerve fibers has shown that the axolemma has a highly differentiated structure. The node is characterized by a high concentration of intramembranous particles, primarily in the E fracture face, which may represent the sodium channels known to be concentrated there, and the paranodal axolemma is characterized by a distinctive paracrystalline pattern that corresponds to the intercellular junction formed with the terminal “loops” of myelin lamellae. Studies of myelin formation in normal animals and of myelin-deficient mutant animals indicate that the development of these axolemmal specializations is profoundly influenced by the associated myelinforming cells. The present study considers whether or not nodal or paranodal specializations that have already formed persist after demyelination.In order to investigate this question, specimens of peripheral nerves were examined following exposure to an antiserum to galactocerebroside (GC), which is known to cause a predictable series of changes leading to demyelination. Freeze-fracture replicas of rat spinal roots exposed to anti-GC serum in situ for six hours showed marked changes in the paranodal axolemma.

Sodium and potassium channels in regenerating and developing mammalian myelinated nerves

1982 ◽  
Vol 215 (1200) ◽  
pp. 273-287 ◽  
Keyword(s):  
Potassium Channels ◽  
Action Potential ◽  
Sodium Channels ◽  
Unit Length ◽  
Nerve Fibres ◽  
Myelinated Nerve ◽  
Complementary Distribution ◽  
Myelinated Nerves ◽  
Sodium And Potassium ◽  
Regenerating Nerve

A study has been made of how the normal complementary distribution of sodium and potassium channels in mammalian myelinated nerve fibres (all the sodium channels being in the node with all the potassium channels in the internode) is altered in regenerating and in developing rabbit sciatic nerves. In regenerating nerve fibres, where a marked increase in the number of nodes per unit length occurs, there is a corresponding increase in the sodium channel content (determined from the maximum saturable binding of labelled saxitoxin), consistent with the idea that the number of sodium channels per node remains roughly constant. The use of 4-aminopyridine, which by blocking potassium channels prolongs the action potential, has shown that both in regenerating nerve fibres and in developing nerve fibres potassium currents contribute to the mammalian action potential. In both cases, with the passage of time, the sensitivity to 4-aminopyridine progressively decreases.

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