Gene/Protein Disease Symptom Drug Enzyme Compound
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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) The effects of benzocaine on the ionic currents in the voltage-clamped squid giant axon have been examined under various conditions; intact axons, axons internally perfused with CsF and axons dialysed with tetraethylammonium ions were used. (2) Both the steady state outward (potassium) current and the early transient (sodium) current were reduced by ca. 50% by benzocaine (1 mM). (3) Plots of the changes produced by benzocaine (1 mM) in the Hodgkin-Huxley parameters for the steady state activation (m infinity), the steady state inactivation (h infinity) and the time constants (tau m and tau h) for activation and inactivation of the sodium current are shown. The m infinity and h infinity curves are shifted in positive and negative directions respectively on the voltage axis. The time constants are not greatly affected. (4) In axons in which the sodium current inactivation had been largely removed by treatment with chloramine T, the sodium current was still reduced by ca. 50% by 1 mM benzocaine and the positive shift in activation remained unchanged. (5) The dependence on benzocaine concentration (for less than or equal to 2 mM) of the peak sodium current reduction and the shift in steady state inactivation have been determined. (6) It is concluded that in the squid axon the effects on inactivation are not the main reason for the reduction of the sodium current by benzocaine and that, in common with many other neutral anaesthetics, there are at least two sites at which benzocaine acts.
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PMID:The mechanisms of sodium current inhibition by benzocaine in the squid giant axon. 244 18

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

1. Axons perfused with a K-free solution containing 300 mM-NaF + sucrose to maintain isotonicity (referred to as 300 mM-NaF) and placed in K-free artificial sea-water usually depolarized spontaneously to around 0 mV. The membrane could be hyperpolarized to -70 to -100 mV with a small inwardly directed current; in one experiment the holding current was measured and was found to be less than 20 muA/cm(2).2. Membrane currents associated with a step depolarization from a potential which varied from -70 to -100 mV showed three phases: (a) an initial capacitative transient, (b) an early current which was inward for small depolarizations and outward for large ones, (c) a smaller maintained current. The currents in (b) and (c) are considered to be carried by Na ions since they both reversed direction at the same potential which was on the average within 0.3 mV of the equilibrium potential for Na ions, 10.4 mV at 0 degrees C and 11 mV at 16.5 degrees C, as estimated from measurements made with a cation-sensitive glass electrode.3. The instantaneous current-voltage relation was determined at the time of peak current and at the end of a long prepulse when the current had reached a steady level. In both cases the curve was approximately linear with a slight deviation at negative potentials.4. Prepulses, lasting 11-48 msec, to a potential of 33-64 mV (0-3.5 degrees C) produced a shift in the equilibrium potential of 0.6-3.3 mV. This small change can be accounted for by assuming that Na ions accumulate in the Frankenhaeuser-Hodgkin space.5. Both peak and steady-state components of Na current were blocked by tetrodotoxin (10(-7) g/ml.) in the external solution.6. The values of peak and steady-state Na conductance were strongly voltage-dependent for V less than -20 mV; for V more negative than -40 mV the peak and steady-state values increased e-fold for a change in potential of 4 and 6-8 mV respectively. At positive potentials the peak conductance was relatively independent of potential, whereas the steady-state curve showed an increase; at 50 mV the steady-state conductance was on the average 0.44 times the peak value for temperatures -0.3 to 4 degrees C and 0.24 times the peak value for a temperature of 16.5 degrees C.7. Following an 18-164 min perfusion period with 300 mM-NaF, the delayed K currents with 300 mM-KF were reduced in amplitude to less than one-tenth the initial level. This apparent removal of the delayed rectifier was not accompanied by any significant change in either the relation between peak early current and voltage or the associated equilibrium potential.8. In an experiment in which tetrodotoxin was used to block the early channel, K currents were determined before and after NaF perfusion. In both cases the kinetics on depolarization followed the Hodgkin-Huxley n(4) relationship and the rate constants were similar, although after NaF perfusion the amplitude was reduced to 0.07 times the control level.9. In axons perfused with 300 mM-KF, following removal of the delayed rectifier by 300 mM-NaF, the ratio of steady-state Na current: peak Na current was estimated to be about half the value obtained with NaF. A similar decrease was obtained in an axon which was perfused with 300 mM-CsF; on subsequent perfusion with 300 mM-KF, following 35 min with CsF, about half the original delayed current was present.10. The general conclusion is that in axons perfused with 300 mM-NaF the Na conductance is not fully inactivated by depolarizations which last for tens of milliseconds. The maintained component may underlie the plateau phase of long lasting action potentials which have been recorded under similar conditions.
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PMID:Sodium and potassium currents in squid axons perfused with fluoride solutions. 550 Oct 55

We have studied the effect of N-bromoacetamide (NBA) on the behavior of single sodium channel currents in excised patches of rat myotube membrane at 10 degree C. Inward sodium currents were activated by voltage steps from holding potentials of about -100 mV to test potentials of -40 mV. The cytoplasmic-face solution was isotonic CsF. Application of NBA or pronase to the cytoplasmic face of the membrane irreversibly removed sodium channel inactivation, as determined by averaged single-channel records. Teh lifetime of the open channel at -40 mV was increased about 10-fold by NBA treatment without affecting the amplitude of single-channel currents. A binomial analysis was used both before and after treatment to determine the number of channels within the excised patch. NBA was shown to have little effect on activation kinetics, as determined by an examination of both the rising phase of averaged currents and measurements f the delay between the start of the pulse and the first channel opening. Our data support a kinetic model of sodium channel activation in which the rate constant leading back from the open state to the last closed state is slower than expected from a strict Hodgkin-Huxley model. The data also suggest that the normal open-channel lifetime is primarily determined by the inactivation process in the voltage range we have examined.
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PMID:Effect of N-bromoacetamide on single sodium channel currents in excised membrane patches. 628 57

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