Inactivation of the Sodium Current in Myxicola Giant Axons

132

SUMMARY1. Sodium currents and fluctuations of sodium currents were measured in myelinated fibres of rat sciatic nerve under voltage clamp at 20 'C.2. Relaxations of sodium currents during various test potentials were recorded in the presence of 6 nM-TTX in the extracellular solution. The activation of sodium currents at low depolarizations could be described with the m2 formulation. At increasing potentials higher powers of m up to 4 were required. The mid-point of the PNa(E) curve was located near E = -32 mV. Sodium inactivation during various depolarizations developed in two phases.3. The resistance in series with the nodal membrane was calculated from peak sodium currents without and with 6 nM-TTX in the extracellular solution. The resistance varied between different fibres and ranged between 190 and 620 k.Q.4. From peak sodium currents at the same membrane potential without and in the presence of TTX an apparent equilibrium dissociation constant of 1-6 nm was calculated for TTX binding to sodium channels.5. The conductance y and the number No (corrected for series-resistance effects) of sodium channels were evaluated from ensemble average values of the mean sodium current and the variance of sodium-current fluctuations at the beginning of a test pulse. The mean values were y = 14-5 pS, No = 21,000 per node.6. The spectral density of stationary sodium-current fluctuations exhibited two relaxation components whose time constants were comparable to those of sodium activation and inactivation. At low depolarizations the variance produced by inactivation fluctuations was larger than predicted by the m3 . h formulation.7. It is concluded that individual sodium channels of rat and frog nerve have similar gating properties. In mammalian nodes the number of sodium channels is lower and the single-channel conductance higher than in amphibian nodes.

Section: Discussionmentioning

confidence: 71%

Sodium currents and sodium‐current fluctuations in rat myelinated nerve fibres

Neumcke

Stämpfli

1982

132

“…This was confirmed by Chandler,Hodgkin & Meves (I965) on perfused squid axons. However, a sigmoid time course with a pronounced initial delay was found by Goldman & Schauf (1972) on Myxicola axons and by Bezanilla & Armstrong (1977) on perfused squid axons. The question whether the time course of inactivation is exponential or sigmoid is related to the question whether activation and inactivation are independent or coupled processes (see Meves, 1978, for review).…”

Section: Introductionmentioning

confidence: 79%

“…By contrast, Bezanilla & Armstrong (1977) and Goldman & Schauf (1972) had concluded that inactivation follows a sigmoid time course with a pronounced initial delay. Bezanilla & Armstrong used a conditioning pulse immediately followed by a test pulse.…”

Section: Discussionmentioning

confidence: 95%

See 1 more Smart Citation

The time course of sodium inactivation in squid giant axons.

Gillespie¹,

Meves²

1980

SUMMARY1. The time course of Na inactivation was studied in intact and perfused squid giant axons under voltage-clamp conditions.2. The pulse programme consisted of a conditioning pulse of varying duration, followed after an interval of 3-8 msec by a test pulse. The measurements were done in sea water with 1/3 or 1/5 of the normal Na concentration. In most experiments a 100 ssec conditioning pulse was sufficient to reduce INa peak elicited by the test pulse. In some experiments even a 50,sec conditioning pulse produced a clear reversible decrease of INa peak, We conclude that the upper limit for an initial delay in the development of inactivation is 50-100 ,usec; this applies to temperatures between 0 and 13 C and membrane potentials between -40 and 15 mV. The decrease of INa peak with increasing duration of the conditioning pulse was consistent with an exponential decay starting at 50 or 100 Itsec.3. With large Na currents in full Na sea water the time course of inactivation became sigmoid. This is attributed to a long-lasting tail of inward current which follows the conditioning pulse and produces a voltage drop across the series resistance.4. If the conditioning pulse and the test pulse were not separated by an interval,

“…A delay in the onset of inactivation has also been claimed for Myxicola axons (Goldman & Schauf, 1972;Schauf & Davis, 1975), for myelinated frog fibres (Peganov, 1973), and for frog skeletal muscle fibres (Campbell & Hille, 1976). In contrast, Chandler, Hodgkin & Meves (1965), Gillespie & Meves (1980) and Dodge (1963), performing two-pulse experiments on perfused squid giant axons and on nodes of Ranvier, respectively, did not detect a delayed onset of inactivation.…”

Section: Introductionmentioning

confidence: 88%

Development of sodium permeability inactivation in nodal membranes.

Kniffki¹,

Siemen²,

Vogel³

1981

SUMMARY1. The time course of inactivation of the sodium permeability was studied in myelinated nerve fibres of Xenopu8 laevi8 using the voltage-clamp technique of Nonner (1969). The potassium currents were blocked by 10 mM-tetraethylammonium chloride (TEA). The remaining currents were corrected for leakage and capacity currents.2. The decay of the sodium current was double-exponential confirming Chiu's (1977) findings. The slower time constant was observed in TEA-free solutions by clamping to VK in high potassium concentrations.3. The fast time constant was similar to Th of Frankenhaeuser (1960), whereas the slower time constant was about four times larger and also decreased with increasing depolarization.4. Arrhenius plots of both time constants can be well approximated by straight lines for temperatures between 0 and 25 'C.5. The entire sodium current induced by single voltage-clamp pulses was fitted by a non-linear least-square routine to the Frankenhaeuser-Huxley equations extended by Chiu's three-state kinetics. With rare exceptions for potentials between 37 and 70 mV the fit was better without a delay in the onset of the inactivation of the sodium current.6. The time course of inactivation was also studied in two-pulse experiments where a prepulse of varying duration was directly followed by a test pulse. The peak sodium currents were normalized by the associated peak currents without a prepulse.7. The relative peak sodium current as a function of the prepulse duration had a sigmoid time course. The early deviation from an exponential decay is due to the activation arising during the prepulse and is implicit in the classical equations quoted above. It is therefore not necessarily a sign of a delay in the inactivation process.8. To eliminate errors due to activation in two-pulse experiments, the decaying part of the test sodium currents was extrapolated back to the onset of the test pulse. These current values at t = 0 plotted as a function of the prepulse duration revealed no delay at the beginning of inactivation. Within the accuracy of our measurements a possible delay of more than 100 #usec (at 5-10 0C) could be excluded.