The time course of sodium inactivation in squid giant axons.

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.

Section: Double Exponential Decay Of Inactivationmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Development of sodium permeability inactivation in nodal membranes.

Kniffki¹,

Siemen²,

Vogel³

1981

“…In some cells there was evidence for a second exponential decline of long time constant as described by Shakhovalov (1977), whereas in others the currents appeared to reach a steady value with a single exponential (cf. Akaike et al 1978;Adams & Gage, 1979 (Gillespie & Meves, 1980 in control current size over the course of the experiment measurements were bracketed with controls (no prepulse) and current during the test pulse is expressed relative to that in the absence of a prepulse (V2/12(0)). Inward current during the test pulse declined exponentially with increasing prepulse duration with r = 58 msec, which is similar to values obtained at the same potential from the decline of inward currents.…”

Section: Ca Current Inactivationmentioning

confidence: 99%

Calcium current inactivation in identified neurones of Helix aspersa.

Plant¹,

Standen²

1981

SUMMARY1. A two-electrode voltage clamp method was used to study Ca inward currents in identified Helix aspersa neurones bathed in 25 mM-Ca, Na-free saline with TEA and 4-AP.2. Inward currents were blocked by CdCl2. In Cd delayed outward currents appeared at + 30 mV. When two identical depolarizations were separated by a gap inward current turned off to the same level during the two pulses up to + 20 mV; above this potential the records cross over.3. The turn-off of inward current at potentials up to + 20 mV was not affected by 0-2 mM-quinine, which reduced outward currents at more depolarized potentials. Inward currents declined exponentially over the first 100 msec with a time constant around 60 msec at 0 mV. Double-pulse experiments gave the same time course of turn-off. 4. When Ca inward current was reduced by lowering [Ca]. or by partial block by Cd the rate and extent of turn-off was reduced.5. The inactivation curve (obtained using a double pulse with gap method) was U-shaped. The curve was not significantly changed by addition of quinine (0-2 mM) or by changing test pulse size.6. Recovery of inward currents after a depolarizing prepulse was a doubleexponential process, with time constants of 120 msec and 9-4 see at 10-11 C.7. Our results are discussed in terms of possible Ca-dependent Ca inactivation and in terms of the possibility of development of an outward Ca-dependent K current.

“…Benzyl alcohol was obtained from Aldrich (gold label). The sodium concentration of the ASW was often reduced in order to decrease the sodium current and thus the voltage drop across the series resistance (see Gillespie & Meves, 1980). This was achieved by substituting the sodium ion with equimolar amounts of the tetramethyl ammonium ion (TMA+).…”

Section: Methodsmentioning

confidence: 99%

“…at which inactivation was complete was subtracted and the difference (IIpeak -Ioo) was plotted on a logarithmic scale against time. The points fall on a straight line from which the time constant of inactivation (Th) can be calculated (Gillespie & Meves, 1980). Benzyl alcohol normally caused a small reversible decrease in Th.…”

Section: Membrane Currents Under Voltage Clampmentioning

confidence: 99%

The effect of temperature on the nerve‐blocking action of benzyl alcohol on the squid giant axon.

Harper¹,

Macdonald²,

Wann³

1983

SUMMARY1. The action of benzyl alcohol was studied on the voltage-clamped giant axons of Loligo forbesi.2. The depressant effect of 7-5 mM-benzyl alcohol on the action potential amplitude and peak rate of rise was more marked at a low (8 0C) than at a high temperature (16-5 IC). A small depolarization (-5 mV) was also produced. These effects were usually reversible.3. Benzyl alcohol (7 5 mM) selectively depressed the amplitude of the peak early current. The maximum inward current was depressed to 0'65 and 0-67 of the control value at 20 0C and 7 0C respectively. This effect was usually reversible. Benzyl alcohol also depressed the peak inward conductance (gNa but had no effect on the time to peak early current.4. A small reversible decrease in the time constant of inactivation (rh) was caused by benzyl alcohol (7 5 mM). This was usually reversible on washout of the anaesthetic.5. Benzyl alcohol (7 5 mM) had no effect on the time course of activation or the amplitude of the delayed outward current.6. The curve of the steady-state inactivation parameter (hoo) for the Na current against the conditioning membrane potential was shifted by benzyl alcohol in a hyperpolarizing direction (at h. = 0 5 the shift was an average of 3-3 mV and was reversible). Increasing the temperature from 7 to 20 0C shifted the curve in a depolarizing direction by approximately 10 mV.7. The reason for the increased nerve-blocking action of benzyl alcohol at the lower temperature is discussed.