Kinetics of Change in Spike Height During Anodal Polarization of Isolated Single Nerve Fibers

1956 ◽  
Vol 187 (3) ◽  
pp. 549-557 ◽  
Author(s):  
Gordon M. Schoepfle
Keyword(s):  
Membrane Potential ◽  
Time Course ◽  
Sodium Current ◽  
Nerve Fibers ◽  
Time Dependent ◽  
Peak Time ◽  
Axon Membrane ◽  
Membrane Hyperpolarization ◽  
Anodal Polarization ◽  
Sodium Inactivation

The time dependent change in magnitude of the nodal action potential was analyzed as a function of time and of change in membrane potential during brief intervals of anodal polarization. The time course of this function involves an exponential term whose time constant decreases to a limiting value as extent of membrane hyperpolarization is progressively increased. While the time course of change in spike height cannot be correlated with any change in membrane potential induced by the polarization, the kinetics suggest that the sodium inactivation mechanism of Hodgkin and Huxley is sufficient to account for the results obtained. Brief direct current pulses elicit changes of membrane potential during activity which indicate that an augmented change in resistance of the hyperpolarized node is sufficient to account for the time dependent increase in spike height. These findings are consistent with the Hodgkin-Huxley scheme in that hyperpolarization of the squid axon membrane at constant membrane potential inhibits ‘sodium inactivation’ thereby allowing sodium conductance and sodium current to attain greater than normal values at peak time of activity. It is concluded that no change in emf of the membrane need be postulated in order to account for the time dependent increase in spike height during hyperpolarization of normal or depressed nodes.

scholarly journals Interaction of n-alkylguanidines with the sodium channels of squid axon membrane.

1980 ◽  
Vol 76 (3) ◽  
pp. 315-335 ◽  
Author(s):  
G E Kirsch ◽  
J Z Yeh ◽  
J M Farley ◽  
T Narahashi
Keyword(s):  
Sodium Channel ◽  
Sodium Channels ◽  
Sodium Current ◽  
Time Dependent ◽  
Squid Axon ◽  
Axon Membrane ◽  
Inactivation Mechanism ◽  
Hydrophobic Binding ◽  
Sodium Inactivation ◽  
Guanidino Group

The effects of n-alkylguanidine derivatives on sodium channel conductance were measured in voltage clamped, internally perfused squid giant axons. After destruction of the sodium inactivation mechanism by internal pronase treatment, internal application of n-amylguanidine (0.5 mM) or n-octylguanidine (0.03 mM) caused a time-dependent block of sodium channels. No time-dependent block was observed with shorter chain derivatives. No change in the rising phase of sodium current was seen and the block of steady-state sodium current was independent of the membrane potential. In axons with intact sodium inactivation, an apparent facilitation of inactivation was observed after application of either n-amylguanidine or n-octylguanidine. These results can be explained by a model in which alkylguanidines enter and occlude open sodium channels from inside the membrane with voltage-independent rate constants. Alkylguanidine block bears a close resemblance to natural sodium inactivation. This might be explained by the fact that alkylguanidines are related to arginine, which has a guanidino group and is thought to be an essential amino acid in the molecular mechanism of sodium inactivation. A strong correlation between alkyl chain length and blocking potency was found, suggesting that a hydrophobic binding site exists near the inner mouth of the sodium channel.

Kinetics of slow changes in membrane potential induced by direct current polarization of single nerve fibers

1958 ◽  
Vol 196 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Gordon M. Schoepfle
Keyword(s):  
Membrane Potential ◽  
Direct Current ◽  
Time Course ◽  
Nerve Fibers ◽  
Slow Potential ◽  
Slow Drift ◽  
Single Nerve ◽  
Sodium Inactivation ◽  
Kinetics Of ◽  
Limiting Value

A direct current pulse applied to an isolated single fiber of the frog sciatic induces a slow drift in membrane potential which can be described by a single exponential term throughout most of its time course. Both magnitude and time parameter are functions of pre-existent membrane potential. With increasing cathodal polarization the magnitude of the drift approaches a limiting value which is dependent only on the duration of the polarizing pulse. No change in resistance is detectable with brief test transient pulses. In fibers sufficiently hyperpolarized to minimize sodium inactivation it is observed that impulses fired off at any time during the course of the slow potential drift are characterized by identical peak values of membrane potential. This indicates that active firing results in a short circuiting of the mechanism responsible for the slow drift. Whereas the data presented favor a change in some e.m.f. as responsible for the slow drift, there exists strong evidence that the potassium emf remains constant.

scholarly journals Kinetic analysis of pancuronium interaction with sodium channels in squid axon membranes.

1977 ◽  
Vol 69 (3) ◽  
pp. 293-323 ◽  
Author(s):  
J Z Yeh ◽  
T Narahashi
Keyword(s):  
Membrane Potential ◽  
Sodium Channel ◽  
Sodium Channels ◽  
Rate Constant ◽  
Time Course ◽  
Voltage Dependence ◽  
Sodium Current ◽  
Sodium Concentration ◽  
Internal Concentration ◽  
Sodium Inactivation

The interaction of pancuronium with sodium channels was investigated in squid axons. Sodium current turns on normally but turns off more quickly than the control with pancuronium 0.1-1mM present internally; The sodium tail current associated with repolarization exhibits an initial hook and then decays more slowly than the control. Pancuronium induces inactivation after the sodium inactivation has been removed by internal perfusion of pronase. Such pancuronium-induced sodium inactivation follows a single exponential time course, suggesting first order kinetics which represents the interaction of the pancuronium molecule with the open sodium channel. The rate constant of association k with the binding site is independent of the membrane potential ranging from 0 to 80 mV, but increases with increasing internal concentration of pancuronium. However, the rate constant of dissociation l is independent of internal concentration of pancuronium but decreases with increasing the membrane potential. The voltage dependence of l is not affected by changine external sodium concentration, suggesting a current-independent conductance block, The steady-state block depends on the membrane potential, being more pronounced with increasing depolarization, and is accounted for in terms of the voltage dependence of l. A kinetic model, based on the experimental observations and the assumption on binding kinetics of pancuronium with the open sodium channel, successfully simulates many features of sodium current in the presence of pancuronium.

Acute effects of repetitive depolarization on sodium current in chick myocytes

1991 ◽  
Vol 260 (6) ◽  
pp. H1810-H1818
Author(s):  
M. R. Gold ◽  
G. R. Strichartz
Keyword(s):  
Time Course ◽  
Sodium Current ◽  
Complete Recovery ◽  
Acute Effects ◽  
Na Current ◽  
Patch Clamp Technique ◽  
Membrane Hyperpolarization ◽  
Atrial Cells ◽  
Whole Cell Patch Clamp ◽  
Recovery From Inactivation

Acute effects of repetitive depolarization on the inward Na+ current (INa) of cultured embryonic chick atrial cells were studied using the whole cell patch-clamp technique. Stimulation rates of 1 Hz or greater produced a progressive decrement of peak INa. With depolarizations to 0 mV of 150-ms duration, applied at 2 Hz from a holding potential of -100 mV, the steady-state decrement was approximately 20%. The magnitude of this effect increased with stimulation frequency and with test potential depolarization and decreased with membrane hyperpolarization. Analysis of INa kinetics revealed that reactivation was sufficiently slow to preclude complete recovery from inactivation with interpulse intervals less than 1,000 ms. Moreover, reactivation accelerated markedly with membrane hyperpolarization, in parallel with the response to repetitive stimulation. The multiexponential time course of recovery of peak INa from repetitive depolarization was similar to that observed after single stimuli; however, there was a shift toward a greater proportion of current recovering with the slower of two time constants. It is concluded that incomplete recovery from inactivation is responsible for the decrement in INa observed with short interpulse intervals.

Conductance changes underlying a late synaptic hyperpolarization in hippocampal CA3 neurons

1987 ◽  
Vol 58 (1) ◽  
pp. 160-179 ◽  
Author(s):  
J. J. Hablitz ◽  
R. H. Thalmann
Keyword(s):  
Membrane Potential ◽  
Voltage Clamp ◽  
Time Course ◽  
Membrane Potentials ◽  
Resting Membrane Potential ◽  
Extracellular Potassium ◽  
Voltage Sensitivity ◽  
Base Line ◽  
Membrane Hyperpolarization ◽  
Ca3 Neurons

1. Single-electrode current- and voltage-clamp techniques were employed to study properties of the conductance underlying an orthodromically evoked late synaptic hyperpolarization or late inhibitory postsynaptic potential (IPSP) in CA3 pyramidal neurons in the rat hippocampal slice preparation. 2. Late IPSPs could occur without preceding excitatory postsynaptic potentials at the resting membrane potential and were graded according to the strength of the orthodromic stimulus. The membrane hyperpolarization associated with the late IPSP peaked within 140-200 ms after orthodromic stimulation of mossy fiber afferents. The late IPSP returned to base line with a half-decay time of approximately 200 ms. 3. As determined from constant-amplitude hyperpolarizing-current pulses, the membrane conductance increase during the late IPSP, and the time course of its decay, were similar whether measurements were made near the resting membrane potential or when the cell was hyperpolarized by approximately 35 mV. 4. When 1 mM cesium was added to the extracellular medium to reduce inward rectification, late IPSPs could be examined over a range of membrane potentials from -60 to -140 mV. For any given neuron, the late IPSP amplitude-membrane potential relationship was linear over the same range of membrane potentials for which the slope input resistance was constant. The late IPSP reversed symmetrically near -95 mV. 5. Intracellular injection of ethyleneglycol-bis-(beta-aminoethylether)-N,N'-tetraacetic acid or extracellular application of forskolin, procedures known to reduce or block certain calcium-dependent potassium conductances in CA3 neurons, had no significant effect on the late IPSP. 6. Single-electrode voltage-clamp techniques were used to analyze the time course and voltage sensitivity of the current underlying the late IPSP. This current [the late inhibitory postsynaptic current (IPSC)] began as early as 25 ms after orthodromic stimulation and reached a peak 120-150 ms following stimulation. 7. The late IPSC decayed with a single exponential time course (tau = 185 ms). 8. A clear reversal of the late IPSC at approximately -99 mV was observed in a physiological concentration of extracellular potassium (3.5 mM).(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Grayanotoxin, veratrine, and tetrodotoxin-sensitive sodium pathways in the Schwann cell membrane of squid nerve fibers.

1976 ◽  
Vol 67 (3) ◽  
pp. 369-380 ◽  
Author(s):  
J Villegas ◽  
C Sevcik ◽  
F V Barnola ◽  
R Villegas
Keyword(s):  
Membrane Potential ◽  
Cell Membrane ◽  
Schwann Cell ◽  
Nerve Fiber ◽  
Schwann Cells ◽  
Giant Axon ◽  
Nerve Fibers ◽  
Resting Membrane Potential ◽  
External Application ◽  
Axon Membrane

The actions of grayanotoxin I, veratrine, and tetrodotoxin on the membrane potential of the Schwann cell were studied in the giant nerve fiber of the squid Sepioteuthis sepioidea. Schwann cells of intact nerve fibers and Schwann cells attached to axons cut lengthwise over several millimeters were utilized. The axon membrane potential in the intact nerve fibers was also monitored. The effects of grayanotoxin I and veratrine on the membrane potential of the Schwann cell were found to be similar to those they produce on the resting membrane potential of the giant axon. Thus, grayanotoxin I (1-30 muM) and veratrine (5-50 mug-jl-1), externally applied to the intact nerve fiber or to axon-free nerve fiber sheaths, produce a Schwann cell depolarization which can be reversed by decreasing the external sodium concentration or by external application of tetrodotoxin. The magnitude of these membrane potential changes is related to the concentrations of the drugs in the external medium. These results indicate the existence of sodium pathways in the electrically unexcitable Schwann cell membrane of S. sepioidea, which can be opened up by grayanotoxin I and veratrine, and afterwards are blocked by tetrodotoxin. The sodium pathways of the Schwann cell membrane appear to be different from those of the axolemma which show a voltage-dependent conductance.

Function of the Hyperpolarization-Activated Inward Rectification in Nonmyelinated Peripheral Rat and Human Axons

1997 ◽  
Vol 77 (1) ◽  
pp. 421-426 ◽  
Author(s):  
Peter Grafe ◽  
Stefan Quasthoff ◽  
Julian Grosskreutz ◽  
Christian Alzheimer
Keyword(s):  
Action Potential ◽  
Sural Nerve ◽  
Nerve Fibers ◽  
Stimulation Frequency ◽  
Time Dependent ◽  
Inward Rectification ◽  
Organ Bath ◽  
Vagus Nerves ◽  
Membrane Hyperpolarization ◽  
Threshold Electrotonus

Grafe, Peter, Stefan Quasthoff, Julian Grosskreutz, and Christian Alzheimer. Function of the hyperpolarization-activated inward rectification in nonmyelinated peripheral rat and human axons. J. Neurophysiol. 77: 421–426, 1997. The function of time-dependent, hyperpolarization-activated inward rectification was analyzed on compound potentials of nonmyelinated axons in the mammalian peripheral nervous system. Isolated rat vagus nerves and fascicles of biopsied human sural nerve were tested in a three-chambered, Vaseline-gap organ bath at 37°C. Inward rectification was assessed by recording the effects of long-lasting hyperpolarizing currents on electrical excitability with the use of the method of threshold electrotonus (program QTRAC, copyright Institute of Neurology, London, UK) and by measuring activity-dependent changes in conduction velocity and membrane potential. Prominent time-dependent, cesium-sensitive inward rectification was revealed in rat vagus and human sural nerve by recording threshold electrotonus to 200-ms hyperpolarizing current pulses. A slowing of compound action potential conduction was observed during a gradual increase in the stimulation frequency from 0.1 to 3 Hz. Above a stimulation frequency of 0.3 Hz, this slowing of conduction was enhanced during bath application of 1 mM cesium. Cesium did not alter action potential waveforms during stimulation at frequencies <1 Hz. Cesium-induced slowing in action potential conduction was correlated with membrane hyperpolarization. The hyperpolarization by cesium was stronger during higher stimulation frequencies and small in unstimulated nerves. These data show that a cesium-sensitive, time-dependent inward rectification in peripheral rat and human nonmyelinated nerve fibers limits the slowing in conduction seen in such axons at action potential frequencies higher than ∼0.3 Hz.

scholarly journals Effects of Internal Divalent Cations on Voltage-Clamped Squid Axons

1974 ◽  
Vol 63 (6) ◽  
pp. 675-689 ◽  
Author(s):  
Ted Begenisich ◽  
Carl Lynch
Keyword(s):  
Time Course ◽  
Voltage Dependence ◽  
Divalent Cations ◽  
Sodium Current ◽  
Ionic Currents ◽  
Zinc Concentrations ◽  
Sodium Inactivation ◽  
Kinetics Of ◽  
Internal Calcium ◽  
Reversible Reduction

We have studied the effects of internally applied divalent cations on the ionic currents of voltage-clamped squid giant axons. Internal concentrations of calcium up to 10 mM have little, if any, effect on the time-course, voltage dependence, or magnitude of the ionic currents. This is inconsistent with the notion that an increase in the internal calcium concentration produced by an inward calcium movement with the action potential triggers sodium inactivation or potassium activation. Low internal zinc concentrations (∼1 mM) selectively and reversibly slow the kinetics of the potassium current and reduce peak sodium current by about 40% with little effect on the voltage dependence of the ionic currents. Higher concentrations (∼10 mM) produce a considerable (ca. 90%) nonspecific reversible reduction of the ionic currents. Large hyperpolarizing conditioning pulses reduce the zinc effect. Internal zinc also reversibly depolarizes the axon by 20–30 mV. The effects of internal cobalt, cadmium, and nickel are qualitatively similar to those of zinc: only calcium among the cations tested is without effect.

scholarly journals Contribution of Particle-Induced Lysosomal Membrane Hyperpolarization to Lysosomal Membrane Permeabilization

2021 ◽  
Vol 22 (5) ◽  
pp. 2277
Author(s):  
Tahereh Ziglari ◽  
Zifan Wang ◽  
Andrij Holian
Keyword(s):  
Membrane Potential ◽  
Time Course ◽  
Causal Relation ◽  
Underlying Mechanism ◽  
Membrane Permeabilization ◽  
Lysosomal Membrane ◽  
Early Event ◽  
Inflammasome Activation ◽  
Membrane Hyperpolarization ◽  
Lysosomal Membrane Permeabilization

Lysosomal membrane permeabilization (LMP) has been proposed to precede nanoparticle-induced macrophage injury and NLRP3 inflammasome activation; however, the underlying mechanism(s) of LMP is unknown. We propose that nanoparticle-induced lysosomal hyperpolarization triggers LMP. In this study, a rapid non-invasive method was used to measure changes in lysosomal membrane potential of murine alveolar macrophages (AM) in response to a series of nanoparticles (ZnO, TiO2, and CeO2). Crystalline SiO2 (micron-sized) was used as a positive control. Changes in cytosolic potassium were measured using Asante potassium green 2. The results demonstrated that ZnO or SiO2 hyperpolarized the lysosomal membrane and decreased cytosolic potassium, suggesting increased lysosome permeability to potassium. Time-course experiments revealed that lysosomal hyperpolarization was an early event leading to LMP, NLRP3 activation, and cell death. In contrast, TiO2- or valinomycin-treated AM did not cause LMP unless high doses led to lysosomal hyperpolarization. Neither lysosomal hyperpolarization nor LMP was observed in CeO2-treated AM. These results suggested that a threshold of lysosomal membrane potential must be exceeded to cause LMP. Furthermore, inhibition of lysosomal hyperpolarization with Bafilomycin A1 blocked LMP and NLRP3 activation, suggesting a causal relation between lysosomal hyperpolarization and LMP.

Effects of cyanide and dinitrophenol on membrane properties of single nerve fibers

1959 ◽  
Vol 197 (5) ◽  
pp. 1131-1135 ◽  
Author(s):  
Gordon M. Schoepfle ◽  
Floyd E. Bloom
Keyword(s):  
Membrane Potential ◽  
State Level ◽  
Nerve Fibers ◽  
Membrane Properties ◽  
Equilibrium Potential ◽  
Resting Membrane Potential ◽  
Appreciable Change ◽  
Single Nerve ◽  
Sodium Inactivation ◽  
Potassium Exchange

Exposure of frog single nerve fibers to cyanide or to dinitrophenol results in a decline in spike height without change in either the resting membrane potential or in the maximal limiting response obtained during strong hyperpolarization. Effects of cyanide are completely reversible; those of dinitrophenol, only partially so. These data are taken to indicate that cyanide depresses the steady state level of the sodium conductance h factor before it produces any appreciable change in either the sodium or potassium equilibrium potentials as a result of interference with the metabolically linked sodium-potassium exchange mechanism. Strong hyperpolarization is effective in overcoming this ‘sodium inactivation’ in the depressed fiber so that the membrane potential approaches a normal sodium equilibrium potential at peak of activity.

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