Effect of sea anemone toxins on the sodium inactivation process in crayfish axons.

The effect of sea anemone toxins from Parasicyonis actinostoloides and Anemonia sulcata on the Na conductance in crayfish giant axons was studied under voltage-clamp conditions. The toxin slowed the Na inactivation process without changing the kinetics of Na activation or K activation in an early stage of the toxin effect. An analysis of the Na current profile during the toxin treatment suggested an all-or-none modification of individual Na channels. Toxin-modified Na channels were partially inactivated with a slower time course than that of the normal inactivation. This slow inactivation in steady state decreased in its extent as the membrane was depolarized to above -45 mV, so that practically no inactivation occurred at the membrane potentials as high as +50 mV. In addition to inhibition of the normal Na inactivation, prolonged toxin treatment induced an anomalous closing in a certain population of Na channels, indicated by very slow components of the Na tail current. The observed kinetic natures of toxin-modified Na channels were interpreted based on a simple scheme which comprised interconversions between functional states of Na channels. The voltage dependence of Parasicyonis toxin action, in which depolarization caused a suppression in development of the toxin effect, was also investigated.

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Delays in inactivation development and activation kinetics in myxicola giant axons.

The Journal of General Physiology ◽

10.1085/jgp.80.1.83 ◽

1982 ◽

Vol 80 (1) ◽

pp. 83-102 ◽

Cited By ~ 15

Author(s):

L Goldman ◽

J L Kenyon

Keyword(s):

Time Constant ◽

Time Course ◽

Series Resistance ◽

Activation Kinetics ◽

Time To Peak ◽

Exponential Decline ◽

Na Inactivation ◽

The Difference ◽

True Property ◽

Kinetics Of

Na inactivation was studied in Myxicola (two-pulse procedure, 6-ms gap between conditioning and test pulses). Inactivation developed with an initial delay (range 130-817 microseconds) followed by a simple exponential decline (time constant tau c). Delays (deviations from a simple exponential) are seen only for brief conditioning pulses were gNa is slightly activated. Hodgkin-Huxley kinetics with series resistance, Rs, predict deviations from a simple exponential only for conditioning pulses that substantially activate gNa. Reducing INa fivefold (Tris substitution) had no effect on either tau c or delay. Delay in not generated by Rs or by contamination from activation development. The slowest time constant in Na tails is approximately 1 ms (Goldman and Hahin, 1978) and the gap was 6 ms. Shortening the gap to 2 ms had no effect on either tau c or delay. Delay is a true property of the channel. Delay decreased with more positive conditioning potentials, and also decreased approximately proportionally with time to peak gNa during the conditioning pulse, as expected for sequentially coupled activation and inactivation. In a few cases the difference between Na current values for brief conditioning pulses and the tau c exponential could be measured. Difference values decayed exponentially with time constant tau m. The inactivation time course is described by a model that assumes a process with the kinetics of gNa activation as a precursor to inactivation.

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Effects of Internal Divalent Cations on Voltage-Clamped Squid Axons

The Journal of General Physiology ◽

10.1085/jgp.63.6.675 ◽

1974 ◽

Vol 63 (6) ◽

pp. 675-689 ◽

Cited By ~ 45

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.

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Selective modification of sodium channel gating in lobster axons by 2, 4, 6-trinitrophenol: Evidence for two inactivation mechanisms.

The Journal of General Physiology ◽

10.1085/jgp.66.6.765 ◽

1975 ◽

Vol 66 (6) ◽

pp. 765-779 ◽

Cited By ~ 27

Author(s):

G S Oxford ◽

J P Pooler

Keyword(s):

Time Course ◽

Sodium Currents ◽

Voltage Range ◽

Sodium Conductance ◽

Gap Technique ◽

Voltage Curve ◽

Sucrose Gap ◽

Sodium Inactivation ◽

Kinetics Of ◽

Double Sucrose Gap Technique

Trinitrophernol (TNP) selectively alters the sodium conductance system of lobster giant axons as measured in current clamp and voltage clamp experiments using the double sucrose gap technique. TNP has no measurable effect on potassium currents but reversibly prolongs the time-course of sodium currents during maintained depolarizations over the full voltage range of observable currents. Action potential durations are increased also. Tm of the Hodgkin-Huxley model is not markedly altered during activation of the sodium conductance but is prolonged during removal of activation by repolarization, as observed in sodium tail experiments. The sodium inactivation versus voltage curve is shifted in the hyperpolarizing direction as is the inactivation time constant curve, measured with conditioning voltage steps. This shift speeds the kinetics of inactivation over part of the same voltage range in which sodium currents are prolonged, a contradiction incompatible with the Hodgkin-Huxley model. These results are interpreted as support for a hypothesis of two inactivation processes, one proceeding directly from the resting state and the other coupled to the active state of sodium conductance.

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

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1958.196.1.1 ◽

1958 ◽

Vol 196 (1) ◽

pp. 1-7 ◽

Cited By ~ 3

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.

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Kinetics of veratridine action on Na channels of skeletal muscle.

The Journal of General Physiology ◽

10.1085/jgp.87.1.1 ◽

1986 ◽

Vol 87 (1) ◽

pp. 1-24 ◽

Cited By ~ 57

Author(s):

J B Sutro

Keyword(s):

Time Constant ◽

Time Course ◽

Voltage Dependence ◽

Na Channels ◽

H Infinity ◽

Tail Current ◽

Time Integral ◽

Activation Gating ◽

Chloramine T ◽

Kinetics Of

Veratridine bath-applied to frog muscle makes inactivation of INa incomplete during a depolarizing voltage-clamp pulse and leads to a persistent veratridine-induced Na tail current. During repetitive depolarizations, the size of successive tail currents grows to a plateau and then gradually decreases. When pulsing is stopped, the tail current declines to zero with a time constant of approximately 3 s. Higher rates of stimulation result in a faster build-up of the tail current and a larger maximum value. I propose that veratridine binds only to open channels and, when bound, prevents normal fast inactivation and rapid shutting of the channel on return to rest. Veratridine-modified channels are also subject to a "slow" inactivation during long depolarizations or extended pulse trains. At rest, veratridine unbinds with a time constant of approximately 3 s. Three tests confirm these hypotheses: (a) the time course of the development of veratridine-induced tail currents parallels a running time integral of gNa during the pulse; (b) inactivating prepulses reduce the ability to evoke tails, and the voltage dependence of this reduction parallels the voltage dependence of h infinity; (c) chloramine-T, N-bromoacetamide, and scorpion toxin, agents that decrease inactivation in Na channels, each greatly enhance the tail currents and alter the time course of the appearance of the tails as predicted by the hypothesis. Veratridine-modified channels shut during hyperpolarizations from -90 mV and reopen on repolarization to -90 mV, a process that resembles normal activation gating. Veratridine appears to bind more rapidly during larger depolarizations.

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Influence of Radioiodine Therapy on Urinary Iodine Excretion

Nuklearmedizin ◽

10.1055/s-0038-1632337 ◽

1998 ◽

Vol 37 (03) ◽

pp. 107-112 ◽

Cited By ~ 1

Author(s):

I. Lauer ◽

M. Bähre ◽

E. Richter ◽

B. Melier

Keyword(s):

Time Course ◽

Radioiodine Therapy ◽

Urinary Iodine ◽

Target Volume ◽

Urinary Iodine Excretion ◽

Urinary Creatinine ◽

Iodine Excretion ◽

Kinetics Of ◽

Persistent Elevation ◽

Benign Thyroid

Summary Aim: In 214 patients with benign thyroid diseases the time-course of urinary iodine excretion (UIE) was investigated in order to identify changes after radioiodine therapy (RITh). Method: UIE was measured photometrically (cerium-arsenite method) and related to urinary creatinine on the first and last day of the radioiodine test and then three days, seven days, four weeks, and six months after 1311 administration. Results: As compared with the level found immediately before radioiodine therapy, median UIE had almost doubled four weeks after therapy and was still significantly elevated six months after therapy. This increase correlated significantly with the target volume as measured by scintigraphy and sonography. Conclusions: The persistent elevation of UIE for months after RITh is a measure of treatment-induced damage to thyrocytes. Therefore, in view of the unfavourable kinetics of iodine that follow it, RITh should if possible be given via a single-dose regime.

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Cognitive dysfunction in amyotrophic lateral sclerosis: can we predict it?

Neurological Sciences ◽

10.1007/s10072-021-05188-0 ◽

2021 ◽

Author(s):

Fabiola De Marchi ◽

◽

Claudia Carrarini ◽

Antonio De Martino ◽

Luca Diamanti ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Time Course ◽

Neurodegenerative Disorder ◽

Early Stage ◽

Multisystem Disorder ◽

Behavioral Impairment ◽

Behavioral Impairments ◽

Als Patients ◽

Disease Stages ◽

Lateral Sclerosis

Abstract Background and aim Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the degeneration of both upper and lower motoneurons in the brain and spinal cord leading to motor and extra-motor symptoms. Although traditionally considered a pure motor disease, recent evidences suggest that ALS is a multisystem disorder. Neuropsychological alterations, in fact, are observed in more than 50% of patients: while executive dysfunctions have been firstly identified, alterations in verbal fluency, behavior, and pragmatic and social cognition have also been described. Detecting and monitoring ALS cognitive and behavioral impairment even at early disease stages is likely to have staging and prognostic implications, and it may impact the enrollment in future clinical trials. During the last 10 years, humoral, radiological, neurophysiological, and genetic biomarkers have been reported in ALS, and some of them seem to potentially correlate to cognitive and behavioral impairment of patients. In this review, we sought to give an up-to-date state of the art of neuropsychological alterations in ALS: we will describe tests used to detect cognitive and behavioral impairment, and we will focus on promising non-invasive biomarkers to detect pre-clinical cognitive decline. Conclusions To date, the research on humoral, radiological, neurophysiological, and genetic correlates of neuropsychological alterations is at the early stage, and no conclusive longitudinal data have been published. Further and longitudinal studies on easily accessible and quantifiable biomarkers are needed to clarify the time course and the evolution of cognitive and behavioral impairments of ALS patients.

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Changes in J chain and mu chain RNA expression as a function of B cell differentiation.

Journal of Experimental Medicine ◽

10.1084/jem.160.3.877 ◽

1984 ◽

Vol 160 (3) ◽

pp. 877-892 ◽

Cited By ~ 61

Author(s):

G Lamson ◽

M E Koshland

Keyword(s):

B Cell ◽

Time Course ◽

Rna Synthesis ◽

Rna Expression ◽

B Cell Differentiation ◽

Activated Lymphocytes ◽

J Chain ◽

Pattern Characteristic ◽

Kinetics Of ◽

Lymphoid Cell Lines

The time course of differentiative events in the pentamer IgM response was examined by following the expression of J chain and mu chain RNA and their protein products in mitogen-stimulated lymphocytes. The analyses showed that the shift to mus RNA synthesis begins shortly after stimulation and precedes proliferation of the cells and any increase in mu RNA levels. In contrast, expression of J chain RNA and the amplification of J chain and mus message are late events that coincide with a phase of rapid proliferation and with the secretion of pentamer IgM antibody. The kinetics of J and mu chain RNA expression observed in normal lymphocytes were supported by analyses of lymphoid cell lines. B lymphomas were found to display the RNA pattern characteristic of early-activated lymphocytes, i.e., a partial shift to mus RNA production and no J chain RNA, whereas IgM-secreting lines resembled late-activated lymphocytes in their expression of high levels of both mus and J chain mRNA. Moreover, the kinetics of J and mus chain RNA expression correlates with the sequential action of B cell lymphokines in the induction of the pentamer IgM response. This correlation suggests that the successive differentiative changes are triggered by successive membrane stimuli.

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Dynamic coupling among neocortical neurons during evoked and spontaneous spike-wave seizure activity

Journal of Neurophysiology ◽

10.1152/jn.1994.72.5.2051 ◽

1994 ◽

Vol 72 (5) ◽

pp. 2051-2069 ◽

Cited By ~ 87

Author(s):

M. Steriade ◽

F. Amzica

Keyword(s):

Cortical Neurons ◽

Time Course ◽

Early Stage ◽

Field Potential ◽

Time Lags ◽

Temporal Relations ◽

Intracellular Recordings ◽

Field Potentials ◽

Thalamic Nuclei ◽

Spike Wave

1. We investigated the development from patterns of electroencephalogram (EEG) synchronization to paroxysms consisting of spike-wave (SW) complexes at 2–4 Hz or to seizures at higher frequencies (7–15 Hz). We used multisite, simultaneous EEG, extracellular, and intracellular recordings from various neocortical areas and thalamic nuclei of anesthetized cats. 2. The seizures were observed in 25% of experimental animals, all maintained under ketamine and xylazine anesthesia, and were either induced by thalamocortical volleys and photic stimulation or occurred spontaneously. Out of unit and field potential recordings within 370 cortical and 65 thalamic sites, paroxysmal events occurred in 70 cortical and 8 thalamic sites (approximately 18% and 12%, respectively), within which a total of 181 neurons (143 extracellular and 38 intracellular) were simultaneously recorded in various combinations of cell groups. 3. Stimulus-elicited and spontaneous SW seizures at 2–4 Hz lasted for 15–35 s and consisted of barrages of action potentials related to the spiky depth-negative (surface-positive) field potentials, followed by neuronal silence during the depth-positive wave component of SW complexes. The duration of inhibitory periods progressively increased during the seizure, at the expense of the phasic excitatory phases. 4. Intracellular recordings showed that, during such paroxysms, cortical neurons displayed a tonic depolarization (approximately 10–20 mV), sculptured by rhythmic hyperpolarizations. 5. In all cases, measures of synchrony demonstrated time lags between discharges of simultaneously recorded cortical neurons, from as short as 3–10 ms up to 50 ms or even longer intervals. Synchrony was assessed by cross-correlograms, by a method termed first-spike-analysis designed to detect dynamic temporal relations between neurons and relying on the detection of the first action potential in a spike train, and by a method termed sequential-field-correlation that analyzed the time course of field potentials simultaneously recorded from different cortical areas. 6. The degree of synchrony progressively increased from preseizure sleep patterns to the early stage of the SW seizure and, further, to its late stage. In some cases the time relation between neurons during the early stages of seizures was inversed during late stages. 7. These data show that, although the common definition of SW seizures, regarded as suddenly generalized and bilaterally synchronous activities, may be valid at the macroscopic EEG level, cortical neurons display time lags between their rhythmic spike trains, progressively increased synchrony, and changes in the temporal relations between their discharges during the paroxysms.(ABSTRACT TRUNCATED AT 400 WORDS)

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