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

1. Helix aspersa neurones under voltage clamp generate prolonged outward currents (potassium currents) in response to depolarizing command pulses. 2. The potassium currents recorded from cell A were reversibly reduced 25-50% by 10 mM cobalt ions in the bathing medium; 1 mM lanthanum, 10(-6) g/ml. D-600 and 10(-6) g/ml. iproveratril had similar effects but were only partially reversible. 3. The relationship between the potassium currents and the membrane potential had an "n" shape in normal saline. In calcium-free saline (containing 25 mM magnesium) the potassium currents were reduced and the "n" shape was abolished. The effect of calcium-free saline was readily reversible. 4. The voltage-dependence of the calcium-sensitive potassium currents was similar to that of the "late" calcium channel in squid axons (Baker, Hodgkin & Ridgway, 1971). 5. When cell A was depolarents were made up of two exponentially declining components. The slower of the two components was reduced in calcium-free saline. 6. When cell A was depolarized by 150 mV for 10 msec and then repolarized the "tail" currents were made up of a single rapidly declining component. The reversal potential of this component changed by 58 mV for a tenfold change in the external potassium concentration as predicted by the Nernst equation. 7. The reversal potential of "tail" currents having both components was less sensitive to changes in the external potassium concentration. 8. Tetraethylammonium (TEA) ions blocked both calcium dependent and voltage sensitive potassium currents. Each receptor was found to bind a single molecule of TEA. The dissociaton constant was about 10 mM in each case. 9. The intracellular concentration of ionized calcium was estimated from the potential at which there was no apparent calcium influx (the null point). It was between 3 x 10(-8) M and 8 x 10(-8) M with 10(-2) M calcium in the bathing medium. 10. The null point changed 30 mV for a tenfold change in the external calcium concentration as predicted by the Nernst equation. 11. It is concluded that depolarization of Helix neurones activates two typesof potassium channel. One channel is voltage dependent and highly selective for potassium. Activation of the other channel is dependent on the influx (or injection, see Meech, 1972, 1974a) of calcium. This calcium mediated potassium activation system saturates at high external calcium concentrations and is inhibited by external magnesium ions.
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PMID:Potassium activation in Helix aspersa neurones under voltage clamp: a component mediated by calcium influx. 117 91

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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PMID:Selective modification of sodium channel gating in lobster axons by 2, 4, 6-trinitrophenol: Evidence for two inactivation mechanisms. 119 89

The question of calculating excitation propagation velocity is analyzed on the basis of the Hodgkin-Huxley model. The activation of the sodium current is assumed to be rapid as compared to the rate of potential variation. Because of slow variation of potassium activation and sodium inactivation the dynamics of these processes is assumed to be of negligible effect in the region of impulse velocity formation. By means of pieace-wise linear approximation of thus obtained voltage-current characteristics the characteristics the analytical solution of the problem was found. In two limiting cases this solution coincides with the solutions of Kolmogorov and Scott. The dependence of impulse velocity on parameters is analyzed and illustrated graphically.
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PMID:[Rate of excitation propagation in a reduced Hodgkins-Huxley model. I. Rapid relaxation of the sodium current]. 120 3

The influence of sodium current activation on the value of nerve excitation conduction velocity is investigated on the basis of Hodgkin-Huxley model. The potassium activation and sodium inactivation are considered as slow processes which do not develop to an appreciable extent in the region of conduction velocity formation. The system of equations was derived and solved analytically after neglecting the dependency of sodium relaxation time on potential; the approximation of steady-state sodium activation was also used with the help of Hevyside function. The algebraic equation for conduction velocity was obtained; its solution has a simple analytical form in two limits of rapid and slow sodium current relaxation. The comparison with the experimental data has shown that at not very high temperatures the slow (compared to the potential dynamics) sodium current relaxation approximation is more appropriate. The dependency of impulse velocity on capacitance and conductance of the fiber was analyzed.
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PMID:[Rate of excitation propagation in a reduced Hodgkins-Huxley model. II. Slow relaxation of the sodium current]. 120 76

Spectral analysis (1-1000 Hz) of spontaneous fluctuations of potential and current in small areas of squid (Loligo pealei) axon shows two forms of noise: f-1 noise occurs in both excitable and inexcitable axons with an intensity which depends upon the driving force for potassium ions. The other noise has a spectral form corresponding to a relaxation process, i.e. its asymptotic behavior at low frequencies is constant, and at high frequencies it declines with a slope of -2. This latter noise occurs only in excitable axons and was identified in spectra by (1) its disappearance after reduction of K+ current by internal perfusion with solutions containing tetraethylammonium (TEA+), Cs+ or reduced [Ki+] and (2) its insensitivity to block of Na+ conduction and active transport. The transition frequency of relaxation spectra are also voltage and temperature dependent and relate to the kinetics of K+-conduction in the Hodgkin-Huxley formulation. These data strongly suggest that the relaxation noise component arises from the kinetic properties of K+ channels. The f-1 noise is attributed to restricted diffusion in conducting K+ channels and/or leakage pathways. In addition, an induced K+ conduction noise associated with the binding of TEA+ and triethyldecylammonium ion to membrane sites is described. Measurement of the induced noise may provide an alternative means of characterizing the kinetics of interaction of these molecules with the membrane and also suggests that these and other pharmacological agents may not be useful in identifying noise components related to the sodium conduction mechanism which, in these experiments, appears to be much lower in intensity than either the normal K conduction or induced noise components.
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PMID:Potassium-ion conduction noise in squid axon membrane. 121 78

1. Whole-cell K+ currents contributing to the resting membrane potential and repolarization of the action potential were studied in voltage-clamped parasympathetic neurones dissociated from neonatal rat intracardiac ganglia and maintained in tissue culture. 2. Rat intracardiac neurones had a mean resting membrane potential of -52 mV and mean input resistance of 850 M omega. The current-voltage relationship recorded during slow voltage ramps indicated the presence of both leakage and voltage-dependent currents. The contribution of Na+, K+ and Cl- to the resting membrane potential was examined and relative ionic permeabilities PNa/PK = 0.12 and PCl/PK < 0.001 were calculated using the Goldman-Hodgkin-Katz voltage equation. Bath application of the potassium channel blockers, tetraethylammonium ions (TEA; 1 mM) or Ba2+ (1 mM) depolarized the neurone by approximately 10 mV. Inhibition of the Na(+)-K+ pump by exposure to K(+)-free medium or by the addition of 0.1 mM ouabain to the bath solution depolarized the neurone by 3-5 mV. 3. In most neurones, depolarizing current pulses (0.5-1 s duration) elicited a single action potential of 85-100 mV, followed by an after-hyperpolarization of 200-500 ms. In 10-15% of the neurones, sustained current injection produced repetitive firing at maximal frequency of 5-8 Hz. 4. Tetrodotoxin (TTX; 300 nM) reduced, but failed to abolish, the action potential. The magnitude and duration of the TTX-insensitive action potential increased with the extracellular Ca2+ concentration, and was inhibited by bath application of 0.1 mM Cd2+. The repolarization rate of the TTX-insensitive action potential was reduced, and after-hyperpolarization was replaced by after-depolarization upon substitution of internal K+ by Cs+. The after-hyperpolarization of the action potential was reduced by bath application of Cd2+ (0.1 mM) and abolished by the addition of Cd2+ and TEA (10 mM). 5. Depolarization-activated outward K+ currents were isolated by adding 300 nM TTX and 0.1 mM Cd2+ to the external solution. The outward currents evoked by step depolarizations increased to a steady-state plateau which was maintained for > 5 s. The instantaneous current-voltage relationship, examined under varying external K+ concentrations, was linear, and the reversal (zero current) potential shifted in accordance with that predicted by the Nernst equation for a K(+)-selective electrode. The shift in reversal potential of the tail currents as a function of the extracellular K+ concentration gave a relative permeability, PNa/PK = 0.02 for the delayed outward K+ channel(s).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Resting membrane potential and potassium currents in cultured parasympathetic neurones from rat intracardiac ganglia. 128 80

Using single-electrode voltage clamp, heart interneurons of the medicinal leech were shown to possess both a rapidly inactivating outward current, IA, and a more slowly inactivating outward current, IK. IA and IK could be separated by their voltage sensitivity and kinetic properties. FMRF-NH2 (Phe-Met-Arg-Phe-NH2) modulates IK by shifting both steady state activation and inactivation to more hyperpolarized potentials, but it does not affect the time constants. IA and IK appear to use K+ as a charge carrier; a change in the external [K+] produced a shift in the apparent reversal potential in the direction predicted with potassium as the charge carrier. Both IA and IK are sensitive to tetraethylammonium (TEA) and 4-aminopyridine (4-AP), and TEA and 4-AP both interfere with the effects of FMRF-NH2 on IK. The biophysical properties of IA and of IK in the presence and absence of FMRF-NH2 were incorporated into a Hodgkin-Huxley model of these currents that could reproduce voltage-clamp data. FMRF-NH2 produces two apparently dissimilar effects on the heartbeat rhythm--acceleration and disruption. We suggest that both effects could result from the hyperpolarizing shifts in steady state activation and inactivation of IK.
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PMID:Modulatory effects of FMRF-NH2 on outward currents and oscillatory activity in heart interneurons of the medicinal leech. 134 5

The charge-duration and strength-duration relations for just threshold rectangular stimuli were numerically investigated for the Hodgkin-Huxley axons of different lengths and different membrane capacitances under normal conditions and blockage of the development of accommodative processes. Two linear portions could be distinguished on the charge-duration curve. One of them followed the Weiss law. The other one represented a portion of a straight line passing through the zero point of the coordinates. The slope of the second portion was determined by the charge for very short stimuli (Q0), the slope of the first portion, and the maximum time to excitation (tau max). The rheobase reflected the slope of the second portion. Upon varying the fibre length the slope of the first and the second linear portions and the rheobase changed. The membrane capacitance substantially affected both the value of Q0 (as in the case of myelinated fibres) and the rheobase. The accommodative processes affected the Q0, the slope of the first line, tau max, and, consequently, the rheobase. The effect of potassium activation was stronger than that of sodium inactivation. The slope of the first line, tau max, and the rheobase might be considered more comprehensive indicators of the accommodative processes than the usually used indicators.
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PMID:Threshold stimulation and accommodation of the Hodgkin-Huxley axon. 149 81

The duration and ionic dependence of action potentials are developmentally regulated. Voltage-clamp recordings of amphibian spinal neurons have revealed alterations in five currents. To determine whether the changes in the currents are sufficient to produce the change in action potential duration and ionic dependence, we constructed a Hodgkin-Huxley model of electrical excitability of these neurons. The model shows that the equations describing the voltage-clamped currents of young and mature neurons generate action potentials appropriate in duration and ionic dependence for each developmental stage. Moreover, the observed changes in the currents are quantitatively sufficient to produce the changes in the action potential. The effect of the change in each current is detectable in the model. However, the increase in amplitude of the delayed-rectifier potassium current has the largest effect. The model further shows that changes in action potential duration could be achieved with changes in kinetics rather than amplitude of this current, or with changes in amplitudes of other currents. Thus, although increase in amplitude of the delayed rectifier plays a pivotal role in the maturation of excitability, it is not uniquely positioned to govern the action potential duration.
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PMID:Reconstruction of action potential development from whole-cell currents of differentiating spinal neurons. 160 40

Activation kinetics of the sodium and potassium conductances were re-examined in fresh axons of Loligo forbesi exhibiting very little if any potassium accumulation and a very small leak conductance, special attention being paid to the initial lag phase which precedes the turning-on of the conductances. The axons were kept intact and voltage-clamped at 2-3 degrees C. In all cases, the rising phase of the currents could be fitted with very good accuracy using the Hodgkin-Huxley (1952) equations although, in most cases, the turning-on of the conductance did not coincide with the beginning of the depolarizing test pulse. The delay which separates the change in potential and the turning-on of current (the activation delay) was analyzed quantitatively for different prepulse and pulse potentials. The measured activation delay differed significantly from the delay predicted by the original HH equations. This difference (the 'non-HH delay') varied with prepulse and pulse potentials. For the potassium current, the relationship between the non-HH delay and pulse potential for a constant prepulse was bell shaped, the maximum value (0.7 ms for a prepulse to -80 mV) being reached for about 0 mV. For this same current, the relationship between the non-HH delay and the prepulse potential for a constant pulse potential was sigmoidal, starting from a minimum value of around 0.5 ms at -100 mV and rising to 5 ms at -15 mV. Essentially similar results were obtained for the sodium current although the non-HH delay was three to five times smaller and the dependency upon prepulse potential not significant.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Quantitative analysis of sodium and potassium activation delays in fresh axons of the squid: Loligo forbesi. 169 Oct 86


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