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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. Asymmetries in the early time course of the displacement current passing across the membrane after application of equal voltage-clamp pulses in the two directions have been investigated in the squid giant axon. Before making the measurements, Na current was blocked by removal of external Na and treatment with tetrodotoxin. Potassium current was usually blocked by perfusion with CsF, but some experiments were done with intact axons. A signal averaging technique was used to eliminate the symmetrical components of the membrane current.2. The asymmetrical current had a contribution of appreciable size attributed to the movement of mobile charges or dipoles in the membrane. This was manifested as an outward current rising rapidly to a peak on depolarization of the membrane and then declining exponentially to zero, followed at the end of the pulse by an inward surge of current with a similar time course. There was also a sustained flow of current outwards during the pulse, arising from ionic leakage with a rectifying characteristic.3. The identification of the exponentially changing current component with the displacement of charged particles forming an integral part of the membrane was supported by the demonstration that the total transfer of charge was equal and opposite at the beginning and end of the pulse, that it reached saturation when the internal potential was taken to a sufficient positive value, and that its size was unaffected by temperature, although its time constant had a large temperature coefficient.4. The disposition of the mobile charges in the steady state was shown to obey a Boltzmann distribution. At the midpoint of the distribution curve, the proportion of the charge displaced underwent an e-fold change for a 19 mV change in potential. The effective valency of the particles, that is their actual charge multiplied by the fraction of the electric field acting on them, was therefore 1.3.5. The total quantity of mobile charge was estimated as about 1500 x 10(-12) C for 0.05 cm(2) of membrane, corresponding to some 1900 charges/mum(2).6. The identification of these mobile charges with the gating particles responsible for controlling Na conductance was supported by the findings that (a) their time constants were the same as those of Hodgkin & Huxley's ;m' system, both in absolute magnitude and in their dependence on potential and temperature, (b) the transition potential at which the charges were evenly distributed on the two sides of the membrane also agreed with that for the ;m' system in intact axons, and its value was similarly shifted in a positive direction by a reduction in internal ionic strength or by raising the external Ca concentration, (c) comparison of the steepness of the curves governing on the one hand the steady-state distribution of the mobile charges and on the other the Na conductance, suggested that an effective cooperation of the charges in groups of three was involved, again in excellent agreement with the ;m' system.7. Displacement of the mobile charges was unaffected by external pH over the range 5-8, but preliminary observations showed that 1% procaine reduced the total charge transfer to somewhat less than 40% of the initial value, and roughly halved the time constant.
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PMID:Kinetics and steady-state properties of the charged system controlling sodium conductance in the squid giant axon. 441 38

Power density spectra of electrical fluctuations in potential and current (during voltage clamp) in the steady state, measured from electrically isolated patches of squid axon membrane, contain a noise component that is of the form [1 + (f/f(c))(2)](-1). For potential and temperature changes f(c) = (2pitau(n))(-1), where tau(n) is the Hodgkin-Huxley relaxation time for the potassium channel. These and other data strongly suggest that this noise is due to the potassium ion passage process in the membrane. Furthermore, by comparison of the values of f(c) from relaxation spectra of membrane channel noise with those from calculated (Hodgkin-Huxley equations) power spectra, it is possible to relate and compare channel models that previously could only be applied to macroscopic potassium conductance data. An initial result of this comparison suggests that a two-state (open-closed) conductance model, which is based upon a literal interpretation of the Hodgkin-Huxley equations, is not likely to be correct.
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PMID:Relaxation spectra of potassium channel noise from squid axon membranes. 451 98

The permeability of K channels to various cations is studied in myelinated nerve. Ionic currents under voltage clamp are measured in Ringer solution containing tetrodotoxin and a high concentration of the test ion. Reversal potentials for current in K channels are determined and used with the Goldman-Hodgkin-Katz equation to calculate relative permeabilities. The ratios P(Tl):P(K):P(Rb):P(NHNH4) are 2.3:1.00:0.92:0.13. No other ions are found to be measurably permeant including Li(+), Na(+), Cs(+), methylamine, guanidine, hydrazine, or hydroxylamine. The ratio P(Na)/P(K) is less than 0.01. Potassium conductance is depressed at pH values below 5.0. Leakage conductance is higher in K, Rb, Cs, NH(4), and Tl Ringer than in Na Ringer, but the selectivity sequence probably is not the same as for K channels. The hypothesis is offered that the narrowest part of the K channel is a circle of oxygen atoms about 3 A in diameter with low electrostatic field strength.
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PMID:Potassium channels in myelinated nerve. Selective permeability to small cations. 454 Oct 77

1. Single muscle fibres from frog semitendinosus were subjected to sudden changes in [K](o), while recording membrane potential.2. In agreement with Hodgkin & Horowicz (1960), a sudden increase in [K](o) in normal fibres produced a rapid depolarization (half-time 0.3 sec), whereas a sudden decrease in [K](o) produced a slower repolarization (half-time 2-3 sec).3. Fibres were subjected to ;glycerol-treatment', a procedure which was supposed to produce a functional disconnexion of the T-system from the surface. In these glycerol-treated fibres both depolarization and repolarization induced by changes of [K](o) took place rapidly.4. The results suggest that the slowness of the repolarization in normal fibres is due to a retention of K ions inside the T-tubules.5. Electron microscopical observation of single fibres or bundles of fibres, which have been soaked in a Ringer containing ferritin, revealed that normal fibres contained ferritin particles in the T-system, while glycerol-treated fibres showed no ferritin. Except for the presence of some large vacuoles and some swelling of the T-system, glycerol-treated fibres appeared morphologically normal.6. Prolonged soaking in a high potassium solution produced electrical effects suggesting that K ions can enter the tubules of treated fibres very slowly, in spite of their inaccessibility to ferritin.7. The main effect of glycerol-treatment does not seem to be a total disconnexion of the T-system from the fibre surface, but rather constriction of the T-tubules near their openings to the exterior.
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PMID:Speed of repolarization and morphology of glygerol-treated frog muscle fibres. 454 76

All analysis of the sodium and potassium conductances of Myxicola giant axons was made in terms of the Hodgkin-Huxley m, n, and h variables. The potassium conductance is proportional to n(2). In the presence of conditioning hyperpolarization, the delayed current translates to the right along the time axis. When this effect was about saturated, the potassium conductance was proportional to n(3). The sodium conductance was described by assuming it proportional to m(3)h. There is a range of potentials for which tau(h) and h(infinity) values fitted to the decay of the sodium conductance may be compared to those determined from the effects of conditioning pulses. tau(h) values determined by the two methods do not agree. A comparison of h(infinity) values determined by the two methods indicated that the inactivation of the sodium current is not governed by the Hodgkin-Huxley h variable. Computer simulations show that action potentials, threshold, and subthreshold behavior could be accounted for without reference to data on the effects of initial conditions. However, recovery phenomena (refractoriness, repetitive discharges) could be accounted for only by reference to such data. It was concluded that the sodium conductance is not governed by the product of two independent first order variables.
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PMID:Quantitative description of sodium and potassium currents and computed action potentials in Myxicola giant axons. 468 23

Repetitive response patterns resembling those of tonic receptors were obtained by increasing the potassium system time constant in the Hodgkin-Huxley (H-H) equations. The increase in time constant varied with membrane potential. Calculated spike frequencies varied linearly with the magnitude of the constant current stimulus; in addition, minimum frequencies were greatly reduced, and the frequency range increased. Modification of the maximum ionic conductances, membrane capacitance, and rate constant voltage dependence was found to vary the minimum frequency, current at that frequency, slope, and over-all modulation of the modified responses.
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PMID:Hodgkin-Huxley axon. Increased modulation and linearity of response to constant current stimulus. 505 59

1. Measurements of the instantaneous K current, under voltage clamp, were obtained using paired de- and hyperpolarizing clamp pulse sequences. The instantaneous potassium current-voltage relations so obtained showed constant field type rectification.2. The zero current potential of the instantaneous K current-voltage relation, when examined as a function of the K concentration, [K](o), behaved like a Nernst concentration cell potential for K. It was concluded that during the generation of the delayed current, the membrane shows substantial selectivity for K.3. The equivalent of the ;Frankenhaeuser-Hodgkin space' in Myxicola was found to be more difficult to load with K ions than in squid. The thickness of the space may be taken as effectively about seven times larger than in squid.4. Myxicola axons were found to show little or no long time constant delayed current inactivation as has been described for squid.5. In high [K](o) a negative steady-state conductance was observed which was predictable from the independence principle with a suitable scaling factor.
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PMID:Rectification in instantaneous potassium current-voltage relations in Myxicola giant axons. 509 79

Computations based upon the Hodgkin-Huxley equations and experimental data from squid axons show that ramp functions can be used as commands to a voltage clamp system to selectively observe either the fast (sodium) or slow (potassium) process in axon membranes without chemical separation techniques or computer assistance. Each process is characterized directly (on line) and rapidly (real time) by generating a current-potential curve on an oscilloscope for fast or slow rates of change of membrane potential (ramps). The speed and directness of this method of characterizing each of the essential axonal events permit quantitative measurement of the kinetics of rapid effects on these processes due to various pharmacological agents such as tetrodotoxin and tetraethylammonium ion or other experimental changes in the membrane environment.
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PMID:Direct and rapid description of the individual ionic currents of squid axon membrane by ramp potential control. 549 3

1. A method which permitted control of the membrane potential near the end of a muscle fibre and measurement of an approximation of the membrane current was used to investigate the effects of the tetraethylammonium (TEA) ion on the delayed outward potassium current obtained on depolarizing.2. Assuming R(i) to be 250 Omega cm and a fibre diameter of 80 mu, the mean value for the maximum potassium conductance (g(K)) was 23.2 +/- 3.2 mmho.cm(-2).3. 58 mM-TEA, in two series of experiments, reduced g(K) by about 90%. A concentration-effect relation for TEA in its action on the delayed rectifier could be fitted by a curve for a drug-receptor complex assuming one molecule of TEA to combine reversibly with one receptor, and a dissociation constant of 8 x 10(-3)M.4. TEA tended to shift the threshold for delayed rectification to slightly more negative membrane potentials. TEA caused a similar shift in the relation between n(infinity) and membrane potential, but did not much alter the form of the relation.5. The relation between n(infinity) and membrane potential and between tau(n) (-1) and membrane potential were well fitted by the model of Adrian, Chandler & Hodgkin (1970a) assuming that the Q(10) was 2.5.6. TEA slowed the rate of onset of the delayed potassium currents, decreasing tau(n) (-1) (the reciprocal of the time constant of the fourth power function which described the current's development) by about 80%.7. The inactivation of the delayed current with time was shown to follow a complex time course. A fast phase decays with a time constant of 270 msec and a slow phase with a time constant of 2.3 sec at a membrane potential of + 10 mV.8. The fast phase of the delayed current is much more susceptible to the action of TEA than the slow phase, and these are interpreted in terms of different potassium channels. TEA has little effect on the time constant with which either the fast current or the slow current inactivates.
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PMID:The effect of the tetraethylammonium ion on the delayed currents of frog skeletal muscle. 549 43

1. Membrane currents during step depolarizations were determined by a method in which three electrodes were inserted near the end of a fibre in the frog's sartorius muscle. The theoretical basis and limitations of the method are discussed.2. Measurements of the membrane capacity (C(M)) and resting resistance (R(M)) derived from the current during a step change in membrane potential are consistent with values found by other methods.3. In fibres made mechanically inactive with hypertonic solutions (Ringer solution plus 350 mM sucrose) step depolarizations produced ionic currents which resembled those of nerve in showing (a) an early transient inward current, abolished by tetrodotoxin, which reversed when the depolarization was carried beyond an internal potential of about +20 mV, (b) a delayed outward current, with a linear instantaneous current-voltage relation, and a mean equilibrium potential with a normal potassium concentration (2.5 mM) of -85 mV.4. The reversal potential for the early current appears to be consistent with the sodium equilibrium potential expected in hypertonic solutions.5. The variation of the equilibrium potential for the delayed current (V'(K)) with external potassium concentration suggests that the channel for delayed current has a ratio of potassium to sodium permeability of 30:1; this is less than the resting membrane where the ratio appears to be 100:1. V'(K) corresponds well with the membrane potential at the beginning of the negative after-potential observed under similar conditions.6. The variation of V'(K) with the amount of current which has passed through the delayed channel suggests that potassium ions accumulate in a space of between (1/3) and (1/6) of the fibre volume. If potassium accumulates in the transverse tubular system (T system) much greater variation in V'(K) would be expected.7. The delayed current is not maintained but is inactivated like the early current. The inactivation is approximately exponential with a time constant of 0.5 to 1 sec at 20 degrees C. The steady-state inactivation of the potassium current is similar to that for the sodium current, but its voltage dependence is less steep and the potential for half inactivation is 20 mV rate more positive.8. Reconstructions of ionic currents were made in terms of the parameters (m, n, h) of the Hodgkin-Huxley model for the squid axon, using constants which showed a similar dependence on voltage.9. Propagated action potentials and conduction velocities were computed for various conditions on the assumption that the T system behaves as if it were a series resistance and capacity in parallel with surface capacity and the channels for sodium, potassium and leak current. There was reasonable agreement with observed values, the main difference being that the calculated velocities and rates of rise were somewhat less than those observed experimentally.
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PMID:Voltage clamp experiments in striated muscle fibres. 549 87


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