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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The characteristics of sodium currents (INa) in single frog ventricular cells were studied with the oil gap method. This method improves time- and space-control of the membrane potential under the voltage clamp, thereby making possible accurate analysis of fast events of INa. In this preparation the threshold of INa was about -60 mV and the reversal potential was 58 mV, which is close to the value calculated by the Nernst equation for sodium ions. Because the instantaneous current-voltage (I-V) relationship is linear, the ease of permeation of sodium ions through Na+ channels is well expressed by the chord conductance. The falling phase of INa and the time course of recovery from inactivation follow a time course of single exponential function. The time constants for on- and off-processes of inactivation at the same membrane potential are very close to each other, indicating only a single state of inactivation. Though almost all properties of INa were well described by Hodgkin-Huxley's model, a clear delay of onset of inactivation was demonstrated by two-pulse experiment. In this report the modified kinetics scheme was proposed which can account for both a delay of onset of inactivation development and a falling phase of INa that follows a single exponential time course.
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PMID:An investigation on the inactivation process of sodium currents in single frog ventricular cells. 255 2

1. The calcium currents evoked by membrane depolarization in the mature and intact rat sympathetic neurone have been studied at 37 degrees C using two-electrode voltage-clamp analysis. 2. Under conditions that eliminate Na+ and K+ currents and 5 mM-external Ca2+, inward currents were observed that activated at about -30 mV and reached maximum amplitude between 0 and +10 mV with time-to-peak values (2.7-1.9 ms) decreasing with increasing membrane depolarization. Thereafter, calcium current (ICa) decayed to a virtually zero level with maintained depolarization. Two exponentials were required to describe the total inactivation process. The faster rate (tau = 29.3-17.6 ms) is ten times the slower rate and proved to be only slightly voltage-dependent. Double-pulse experiments gave a similar time course of turn-off. 3. No steady-state inactivation was removed at holding potentials between -40 and -70 mV and indirect data suggest that all the ICa was available at -50 mV. Within the -30 to -50 mV holding potential range no significant modifications either in the final amount of ICa inactivation or in the inactivation time constant values were detected. 4. After an initial 100 ms, recovery from inactivation followed a single-exponential process with a mean time constant value of 1.54 s at -50 mV. 5. The kinetics of ICa observed in this neurone were consistent with the existence of a single class of Ca2+ channels. For times up to 20 ms, ICa is described reasonably well by a Hodgkin-Huxley c2hc scheme. The activation time constant was 0.57 ms close to threshold and 0.29 ms at +30 mV. Deactivation occurred with a similar fast time course. The steady-state value of the variable c was evaluated in the -40 to +20 mV voltage range: 9.9 mV are required to change c infinity e-fold. 6. Following previous analyses, we have formulated a mathematical model which incorporates the present ICa kinetic equations with Hodgkin-Huxley-type gating mechanisms for INa, IA and IK(V) conductances. The Ca2+ load of the neurone proved to be basically an 'off' effect and to be governed by the duration of the action potential falling phase. The model is consistent with the experimental observations indicating that Ca2+ channels probably do not have an important direct electrical function in the sympathetic neurone spike at normal membrane potential levels.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Calcium currents in the normal adult rat sympathetic neurone. 255 30

Myoballs were cultured from biopsies of adult human skeletal muscle. Transient currents through the sodium channels were elicited by depolarizing a myoball membrane with the whole-cell patch-clamp technique. The properties of the sodium channels were determined from the Hodgkin-Huxley parameters (INa max, tau m, tau h, h infinity-curve) derived from these transients. Halothane, when applied at 3.4 mmol/l (approximately 15 kPa), blocked about 50% of the current through the adult, TTX-sensitive sodium channels but had little effect on the current through the juvenile, TTX-insensitive sodium channels. At greater than 12 mmol/l, halothane blocked both channel types completely. The time constants of activation and inactivation were decreased in the presence of 3.4 mmol/l halothane but not enough to account for the decrease of the current amplitude. Halothane shifted the h infinity-curves of both channel types toward more negative potentials by an amount that was roughly proportional to its concentration. Myoballs from a man susceptible to malignant hyperthermia (MH) gave the same results as the controls indicating that the halothane effect on the action potential of MH-susceptible muscle are not mediated by a specific effect on the sodium channels.
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PMID:Differential effects of halothane on adult and juvenile sodium channels in human muscle. 284 55

The experiments were done on voltage-clamped nodes of Ranvier of the frog. The aim was to study the kinetics of sodium current INa and gating current Igat over a large potential range (-92 to -12 mV) and to compare the time constants for the turning-on of INa or Igat with those for the turning-off measured at the same potential. Sodium tail currents were recorded at different postpulse potentials. Inactivation was inhibited by a few min treatment with 0.5 mM chloramine-T (Wang 1984). The sodium permeability was activated by a 0.4 ms pulse from holding potential (-92 mV) to about 0 mV. At the peak of INa the membrane was repolarized to postpulse potentials between -92 and -12 mV. At E greater than -60 mV the tail currents decayed with two time constants, tau 1 and tau 2, reflecting presumably the turning-off and the inactivation of the sodium permeability. The relation between tau 1 and postpulse potential was bellshaped with a maximum at -32 mV. The tail currents could also be fitted by the Hodgkin-Huxley equation with the sodium activation variable m raised to the second or third power. At E less than -50 mV tau m off was equal to 2 tau 1 or 3 tau 1, respectively, whereas at E greater than -25 mV tau m off was equal to tau 1. In addition, the time constant of the turning-on of sodium activation m (tau m on) was determined, assuming INa approximately m2 (with a small initial delay) or INa approximately m3 (without an initial delay). At -22 mV and -12 mV the ratio tau m off/tau m on was close to 1.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Kinetics of sodium current and gating current in the frog node of Ranvier. 348 38

Membrane potential and current were studied in cut end fibres of frog skeletal muscle under current and voltage clamp conditions, by the double sucrose gap technique. Similar action potentials were recorded under current clamp conditions with either the microelectrode or the double sucrose gap techniques. Under voltage clamp conditions, the control of the membrane potential was maintained adequately. The early current was sensitive to both TTX and external Na concentration suggesting that the current was carried by Na ions. Sodium current (INa) was subsequently analysed using the Hodgkin-Huxley formulae. INa half-activation and inactivation occurred at -34 mV and -60 mV, respectively. Na-rich solution applied internally by diffusion through cut ends produced a reduction of INa associated with a shift of the sodium current reversal potential (VNa) towards more negative membrane potentials. This suggested that the sodium electromotive force was reduced by the increase in internal Na content of the fibre. Iodate applied externally changed neither the activation nor the inactivation time courses of INa, but reduced the peak current. Conversely, internally applied by diffusion from the cut end of skeletal muscle fibre, iodate slowed down the time course of INa inactivation and decreased the current peak. In conclusion, the double sucrose gap technique adapted to cut end frog skeletal muscle fibre allows a satisfactory analysis of INa.
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PMID:Voltage-clamp of cut-end skeletal muscle fibre: a diffusion experiment. 349 62

To study the kinetic and steady-state properties of voltage-dependent sodium conductance activation, squid giant axons were perfused internally with either pronase or N-bromoacetamide and voltage clamped. Parameters of activation, tau m and gNa(V), and deactivation, tau Na, were measured and compared with those obtained from control axons under the assumption that gNa oc m3h of the Hodgkin-Huxley scheme. tau m(V) values obtained from the turn-on of INa agree well with control axons and previous determinations by others. tau Na(V) values derived from Na tail currents were also unchanged by pronase treatment and matched fairly well previously published values. tau m(V) obtained from 3 x tau Na(V) were much larger than tau m(V) obtained from INa turn-on at the same potentials, resulting in a discontinuous distribution. Steady-state In (gNa/gNa max - gNa) vs. voltage was not linear and had a limiting logarithmic slope of 5.3 mV/e-fold gNa. Voltage step procedures that induce a second turn-on of INa during various stages of the deactivation (Na tail current) process reveal quasiexponential activation at early stages that becomes increasingly sigmoid as deactivation progresses. For moderate depolarizations, primary and secondary activation kinetics are superimposable. These data suggest that, although m3 can describe the shape of INa turn-on, it cannot quantitatively account for the kinetics of gNa after repolarization. Kinetic schemes for gNa in which substantial deactivation occurs by a unique pathway between conducting and resting states are shown to be unlikely. It appears that the rate-limiting step in linear kinetic models of activation may be between a terminal conducting state and the adjacent nonconducting intermediate.
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PMID:Some kinetic and steady-state properties of sodium channels after removal of inactivation. 616 10

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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PMID:Delays in inactivation development and activation kinetics in myxicola giant axons. 628 38

The time course of the rise in sodium conductance during positive voltage-clamp pulses was measured in squid giant axons perfused with CsF and immersed in low-sodium solutions. The initial transients were eliminated by subtraction of records made after blocking the sodium channels with tetrodotoxin. The value of tau m as defined by Hodgkin & Huxley (1952) passed through a well defined maximum at a membrane potential of about -35 mV. On fitting the initial inflexion in the rise of INa to the expression mXh instead of m3h, the value of X was found to vary from axon to axon between 2.9 and 4.4, with an average of 3.5. For any given axon, X did not vary significantly with pulse potential. Measurements of tau m were made on approaching each value of the membrane potential both from the negative and from the positive side. The cube law kinetics of the Hodgkin-Huxley equations were closely obeyed. Application of a negative prepulse to -180 mV delayed the rise of conductance by 20 musec at 7 degrees C without obviously changing tau m. Comparisons of the voltage dependence of tau m with that of the time constant tau 1 of the fast relaxation of the asymmetry current measured in the same axon, showed that tau 1 was smaller than tau m except at positive potentials, was less steeply voltage-dependent, and reached its maximum at a more positive potential.
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PMID:Kinetics of activation of the sodium conductance in the squid giant axon. 630 31

The kinetics of the TTX sensitive Na+ current (INa) in the slowly adapting lobster stretch receptor neurone were investigated in sub- and near-threshold voltage regions using electrophysiological and pharmacological techniques. In dynamic conditions INa was found to display both fast and slow reactions. These were attributed to a fast Hodgkin-Huxley type of Na activation and inactivation, and a slow type of Na inactivation, respectively. In stationary conditions the voltage dependence of the slow Na inactivation was shifted in a depolarizing direction by increasing, and in a hyperpolarizing direction by decreasing the extracellular Ca++ concentration. From this finding as well as from its kinetic properties the slow Na inactivation was classified as a genuine gating process. The processes of fast Na activation and inactivation were too fast for a dynamic analysis with the recording technique available. An estimate of their stationary voltage dependence could however be obtained in a voltage range from about -80 to about -50 mV. The experimental findings were used for the formulation of a mathematical description of INa in the present preparation based on constant field and state transition theories.
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PMID:Kinetics of the TTX sensitive Na+ current in the slowly adapting lobster stretch receptor neurone. 631 51

The voltage and time-dependence of the tetrodotoxin sensitive, fast sodium current in cardiac muscle is described with the Hodgkin-Huxley formalism using two microelectrode, voltage-clamp data obtained by Ebihara et al. (1980, J. Gen. Physiol., 75:437) from small spherical clusters of tissue-cultured 11-d-old embryonic heart cells. The data chosen from that study for quantitative analysis was obtained at 37 degrees C and in standard tissue-culture medium; it was not smoothed, and the capacitive transient was sufficiently brief to make its removal unnecessary. The sodium current, INa, is considered to be given by the following equation: INa = gNa m3h(V - VNa), where gNa is a constant (23 mS), VNa is the sodium equilibrium potential (29 mV), and m and h are independent, first order, dimensionless variables, which can vary between 0 and 1, as defined by the following differential equations, dm/dt = alpha m(1 - m) - beta mm and dh/dt = alpha h(1 - h) - beta hh, where the rate coefficients, alpha m = [0.32 x (V + 47.13)]/[1 - exp(V + 47.13)] and beta m = 0.08 x exp (-V/11). For potentials more positive than -40 mV, alpha h = 0 and beta h = 1/0.13 (exp [(V + 10.66)/ - 11.1] + 1), and for potentials more negative than -40 mV, alpha h = 0.135 x exp [(-80 - V)/6.8] and beta h = 3.56 x exp (0.079V) + 3.1 x 10(5) exp (0.35V). These functions of potential are similar to those of the squid at 15 degrees C, except that their magnitudes are larger (faster). Using these model equations the membrane current in a membrane patch with and without a series resistance was simulated. For the value of series resistance estimated for the preparation from which the analyzed data were obtained, the effects of series resistance on the shape and magnitude of the inward transient current were found to be minimal. It was concluded that their should be no large errors in the data, even in the absence of complete series resistance compensation.
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PMID:Fast sodium current in cardiac muscle. A quantitative description. 726 Mar 1


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