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F Conti

Publications and source records attributed to F Conti.

At least 253 records · Page 14Linked to original sources

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↗

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↗

Fluorescence polarization studies of squid giant axons stained with N-methylanilinonaphthalenesulfonates.

The polarized components of the extrinsic fluorescence of squid giant axons stained with 2,6-MANS or 1,8-MANS were studied. The polarization properties of the fluorescence changes associated with voltage-clamp pulses were found to be very different from those of the static fluorescence, supporting the notion that the optical changes involve highly oriented membrane adsorbed fluorophores. The theoretical expectations according to this hypothesis are discussed in detail. The experimental results are in good agreement with the theory assuming that possible probes reorientations are soley due to the action of the applied electric field upon the probes electric dipole. The quantitative analysis of the data for 2,6-MANS provides a fairly accurate determination of the orientation of the membrane bound 2,6-MANS molecules responsible for the fluorescence changes. Such orientation appears to be independent of the membrane face exposed to staining. The data for 1,8-MANS indicate a very different orientation of this isomer. The results suggest a profitable use of extrinsic fluorophores for studies of the structural organization of nerve membranes.

Anilino Naphthalenesulfonates↗

Double-blind study of the analgesic effect of indoprofen (K 4277).

In a double-blind study, indoprofen was superior to placebo in decreasing pain in patients with primary and metastatic cancer and with neuralgia. A single oral dose of 200 mg was more active than a 100-mg dose. The preferences of patients proved to be a more sensitive parameter in this study than scores of pain intensity, pain relief, and other related measurements (SPID, TOTPAR, and Peak PID).

Adult↗

Potassium and sodium ion current noise in the membrane of the squid giant axon.

1. The spectral density of current noise power from 20 mm segments of giant axons of the squid Loligo vulgaris has been measured under space-clamp and voltage-clamp conditions. From 4 to 1000 Hz the measured noise is larger by several orders of magnitude than the theoretical thermal noise. The amplifier's noise, which may yield appreciable contributions above 200 Hz, could be evaluated and subtracted from the total noise using direct measurements of the membrane impedance...

Action Potentials↗

Potassium and sodium current noise from squid axon membranes.

Current noise under voltage clamp has been measured from the giant axon of Loligo vulgaris. Relatively large areas (up to 0.4 cm2) were used for these measurements, under standard space clamped conditions. Current noise spectral densities were studied in the range of 0 to 20 C, -100 to -40 mV and in normal, tetrodotoxin, and tetraethylammonium ion solutions. Three components of current noise were found, l/f-noise, and a K and a Na component.

Animals↗