Biomedical subjects

W Nonner

Publications and source records attributed to W Nonner.

27 records · Page 2Linked to original sources

PubMed1976

Asymmetrical displacement current and its relation with the activation of sodium current in the membrane of frog myelinated nerve.

1. Sodium currents (INa) and asymmetrical displacement currents (ID) were measured in the same nerve fibres from Rana esculenta under similar conditions. 2. For exploring possible kinetic and steady state relations between INa and ID the following quantities were compared: (i) the activation of the sodium channels and (ii) the charge displacement of ID. 3. The delay of sodium activation increased after hyperpolarization. A corresponding effect on the displacement of charge was not observed. 4. Upon a small depolarization sodium activation rose slower than the displacement of charge, whereas at large depolarizations sodium activation reached a steady level before the charge displacement. 5. Upon repolarization to various levels between -52 and 12 mV relative to the resting potential, the ratio between the time constants of charge displacement and of sodium tail current varied between 3 and 1. 6. In the steady state the sodium activation was one half at about the same potential as the charge displacement but exhibited a clearly steeper voltage dependence. 7. Blocage of sodium channels with tetrodotoxin did not affect the asymmetrical displacement current. Replacing a part of external Na by tris did not alter the sodijm activation process. 8. The results indicate that the asymmetrical displacement of charge may reflect states of the gating mechanism in sodium channels but cannot be considered as a correlate of the Hodgkin Huxley m variable.

Animals↗

PubMed1976

Measurement of the conductance of the sodium channel from current fluctuations at the node of Ranvier.

Single myelinated nerve fibres of Rana esculenta were investigated under voltage clamp conditions at 13 degrees C. Fluctuations of steady-state membrane current were measured during the last 152 msec of 190-225 msec pulses depolarizing the membrane by 8-48 mV. Noise power spectral densities were calculated in the frequency range of 6-6-6757 Hz. 2. External application of 150 nM tetrodotoxin (TTX) and/or 10 mM tetraethylammonium (TEA) ion reduced the current fluctuations. The difference of current noise spectra measured in the presence and absence of TTX (TEA) was not changed by the presence of TEA (TTX) during both measurements, and was taken as the spectrum of the Na (K) current fluctuations. 3. Residual current noise during application of both TTX and TEA was, except for some excess noise at the low and high frequency ends of the spectrum, similar to the noise measured from a passive nerve model and could be understood in terms of Nyquist noise of the known resistances and the amplifier noise. 4. Na current fluctuation spectra were interpreted as the sum N/f+SNa(f) where SNa(F) represents the spectrum expected for a set of equal, independent Na channels with only two conductance states (open or closed) which follow Hodgkin-Huxley kinetics. With values of hinfinity, tauh and minfinity measured from macroscopic Na currents, the measured spectra were fitted well by optimizing N, SNa(0) and taum. Values of taum obtained by this method were in fair agreement with values found from macroscopic currents. 5. The 1/f component of Na current noise was roughly proportional to the square of the steady-state Na current, I2. The mean value of N/I2 was (1-1 +/- 0-3) X 10(-4). 6. The current carried by a single Na channel was calculated from fitted spectra and steady-state Na currents measured simultaneously with the current fluctuations. The single channel conductance gamma normalized to zero absolute membrane potential was calculated. The average gamma from twelve measurements at depolarizations of 8-40 mV was 7-9 +/- 0-9 pS (S.E. of mean). The apparent value of gamma was smallest with small depolarizations. Variations of the assumed kinetic properties of the model did not drastically affect the single channel conductance. 7. External application of 0-1 mM-Ni ion lengthened taum in the macroscopic currents and in the fluctuation spectra and enhanced both the steady-state Na current and the current fluctuations. In Ni-treated nodes gamma was smaller than in normal nodes.

Animals↗

PubMed1976

Conductance of the sodium channel in myelinated nerve fibres with modified sodium inactivation.

1. Na current fluctuations in nodes of Ranvier were measured under voltage clamp conditions as described in the preceding paper (Conti, Hille, Neumcke, Nonner & Stämpfli, 1976) and analysed in terms of power spectral density calculated for frequencies between 30 Hz and 5 kHz. 2. External (10(-5) g/ml.) Leiurus scorpion venom or Anemonia Toxin II (3 X 10(-5) g/ml.) or internal 20 mM iodate were applied in order to remove or slow down inactivation in part of the Na channels. The treatment increased the steady-state Na current during the noise measurement one-to eight fold over that in normal fibres. 3. Noise spectra were interpreted as the sum of 1/f noise and noise SNa(f) due to all-or-none, open-close transitions of single Na channels. The drug effects on the inactivation could be accounted for either by assuming two populations of channels, one with and one without inactivation, or by postulating a single population with modified inactivation characteristics. 4. Except for an increase in amplitude, the fluctuation spectra SNa(f) were similar to the ones in normal nodes. Again, the time constants taum obtained from the fit of the spectra agreed within a factor of 2 with the values of taum found in the macroscopic Na currents. 5. From the fluctuation spectra, single Na channel conductances gamma of 5-4 +/- 0-4 pS (iodate), 6-7 +/- 0-5 pS (Leiurus) and 7-0 +/- 0-6 pS (Anemonia) were calculated. The value of gamma was not significantly voltage dependent. 6. Our observations indicate that inactivation of Na channels can be modified with at most small effects on the microscopic properties of the activation process and on the conductance of the open channel. They suggest that the h mechanism normally produces all-or-none, open-close changes of conductance.

Animals↗

PubMed1975

Gating currents in the node of Ranvier: voltage and time dependence.

Like the axolemma of the giant nerve fibre of the squid, the nodal membrane of frog myelinated nerve fibres after blocking transmembrane ionic currents exhibits asymmetrical displacement currents during and after hyperpolarizing and depolarizing voltage clamp pulses of equal size. The steady-state distribution of charges as a function of membrane potential is consistent with Boltzmanns law (midpoint potential minus 33.7 mV; saturation value 17200 charges/mum-2). The time course of the asymmetry current and the voltage dependence of its time constant are consistent with the notion that due to a sudden change in membrane potential the charges undergo a first order transition between two configurations. Size and voltage dependence of the time constant are similar to those of the activation of the sodium conductance assuming m-2h kinetics. The results suggest that the presence of ten times more sodium channels (5000/mum-2) in the node of Ranvier than in the squid giant axon with similar sodium conductance per channel (2-3 pS).

Animals↗

PubMed1975

Displacement currents in the node of Ranvier. Voltage and time dependence.

The time course of the membrane currents in the node of Ranvier in which the sodium and potassium conductances have been blocked reveals asymmetries during and after the application of depolarizing and hyperpolarizing voltage-clamp pulses of identical size. Since 1. the integrals of the "on" and "off" current transients were found to be equal and opposite, 2. the change displaced reached saturation (about 140-10-minus 15 C/node) when the internal potential was taken to a sufficiently positive value during the depolarizing pulses and, 3. the size of the charge transferred was unaffected by temperature although its time constant had a large temperature coefficient (Q10 = 2.4), these currents to our opinion must result form charge movements confined to the membrane and, therefore, can be considered as non-liner displacement currents. The steady-state rearrangement of the charges is consistent with a Boltzmann distribution of charges (effective valence z = 1.65) between two configurations characterized by different energy levels. The midpoint potential of the distribution curve is -33.7mV and its maximum slope, kT/ZE, is 14.9 mV. Following changes in membrane potential the charges undergo a first order transition between these states. We propose that these displacement currents arise from a redistribution of the charges involved in the sodium gating system.

Action Potentials↗

PubMed1969