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O Rougier

Publications and source records attributed to O Rougier.

At least 55 records · Page 3Linked to original sources

Analysis of the negative inotropic effect of acetylcholine on frog atrial fibres.

Voltage-clamp experiments have been performed on frog atrial preparations in order to study the mechanism of the inotropic effect of acetylcholine (ACh) at various concentrations. The amplitude of the slow inward current (Is) is reduced even at low ACh concentrations; such low concentrations have little or no effect on potassium permeability. Dose-effect relationships for Is inhibition (Is/Is max) by ACh show a half amplitude dose (K0.5 around 8 X 10(-8) M ACh. The reduction of Is is attributed largely to a decrease of the maximal conductance of the slow channel (gs). Steady-state activation and inactivation parameters are not affected by ACh. Experiments in a Na-free solution (Na replaced by Li ions) or in a Ca-free solution (with EGTA) indicate that the "slow sodium current" is more sensitive to ACh than the "slow Ca current", although these two currents both seem to flow through the slow channel. The decrease of the phasic component of contraction observed in the presence of ACh is very well correlated with the decrease of Is (K0.5 = 8 X 10(-8) M ACh), while the increase of the tonic tension may be related to the outward potassium current induced by high concentrations of ACh. The significant difference between the half amplitude dose (K0.5) observed in the dose effect curves with ACh for Is inhibition (K0.5 = 8 X 10(-8) M) and for ACh-induced extra-current (K0.5 - 10(-6) M) may indicate the presence of two muscarinic receptors.

Acetylcholine↗

[Demonstration of intracellular release of calcium induced by sodium ions in the auricular trabeculae of the frog].

In a Ca-free, Mg-free medium containing EGTA (10-3M) auricular trabecles develop a slow inward current which is a pure sodium current. After 12 min in this medium, it is still possible to obtain a phasic mechanical activity which shows a perfect correlation with the current. This kind of behavior indicates that a mechanism of sodium-induced calcium release is present at the level of some internal sites.

Animals↗

Evidence for an action of sodium ions in the activation of contraction of twitch muscle fibre.

Simultaneous records in current clamp conditions of potential and of contraction of frog skeletal twitch muscle fibre have shown that a part of the contraction directly depends on the intervention of sodium ions (increase in presence of veratrine, decrease in lithium Ringer). The results confirm previous voltage clamp data and suggest a mechanism of sodium induced calcium release.

Action Potentials↗

Existence of a sodium current in the tubular membrane of frog twitch muscle fibre; its possible role in the activation of contraction.

1. The membrane current of frog twitch muscle fibre has been recorded together with contraction in the test gap of a double sucrose gap apparatus. 2. In Ringer, the inward current sometimes shows 2 phases with the same threshold and the same reversal potential: a rapid one (early inward current) and a slower one (late inward current). The mechanical threshold is near the inward current threshold. The amplitude of the contraction increases progressively with depolarizations, without modification of its time to peak. Experiments with variation of the pulse duration and with conditioning depolarization show that a part of the contraction seems to be correlated with the late inward current. 3. Experiments in a sodium free solution, with low TTX concentration, and on glycerol treated fibres show that the late inward current corresponds to a tubular sodium current. 4. A method is described to separate the two phases of inward current. The smooth development of the current-voltage relation of the late inward current, its diminution without modification in time to peak under the action of TTX, and the exponential decay of its tail current all suggest that the tubular membrane potential is sufficiently well controlled. 5. In the experiments where the tubular membrane potential seems to be controlled, a part of the contraction depends on the tubular sodium current, perhaps involving a mechanism of sodium induced calcium release.

Animals↗

The action of acetylcholine on background conductance in frog atrial trabeculae.

The action of acetylcholine (ACh) on membrane potential and currents in frog atrial muscle has been studied with a double sucrose gap technique. The results show the following. 1. ACh induces the development of an extra current, outward at the resting potential, which is dependent on the ACh concentration. 2. The preparation does not show any sign of desensitization. 3. The reversal potential of the current induced by ACh is between 0 and 20 mV more negative than the resting potential and behaves as a K electrode. 4. The mechanism of ACh-induced K conductance presents inward going rectification properties. 5. The delayed outward current is not affected by ACh. However the evolution of its tail current seems to indicate a process of K accumulation related to the ACh-induced current.

Acetylcholine↗

[Electrophysiologic study of the cholinergic receptor of the myocardial membrane].

A double sucrose gap voltage clamp technic has been used to study the extra-current induced by acetylcholine (Iach) on the myocardial membrane on frog atrial trabeculae. I) No desensitization of the Iach current is noted for repeated perfusions of Ach. II) The Iach current is suppressed by atropine. III) The reversal potential Each is more negative than the resting potential --20 mV less than or equal to Each less than or equal to OmV.IV) The relationship Iach/Holding potential for various [K+]o shows a) That Each behaved as a potassium electrode, b) an inward going rectification. These results indicate that the cholinergic receptor might be related with the gk1 channel.

Acetylcholine↗

Kinetic analysis of the delayed outward currents in frog atrium. Existence of two types of preparation.

1. The outward currents underlying delayed rectification have been studied in frog auricular trabeculae with the double sucrose gap method.2. The results obtained in our experimental conditions allow us to discard the hypothesis of an accumulation of ions during the flow of the outward current.3. In most of the cases the delayed current is composed of two components similar to those previously described by Noble & Tsien (1969a, b).4. The first component I(1) is activated with a time constant of about 0.3 sec at the resting potential (E = - 70 mV) and of about 0.75 sec at E = - 5 mV. The steady-state value of the degree of activation (x(1))(infinity) varies from 0 at E = - 90 mV to 1 at E = + 20 mV. The reversal potential is near E = - 80 mV; this current seems to be mainly carried by potassium ions.5. The second component I(2) is very slowly activated, with a time constant of 3.5 sec at E = - 70 mV and of 5 sec at E = - 5 mV. The steady-state value of the degree of activation (x(2))(infinity) varies from 0 at E = - 40 mV to 1 at E = + 25 mV. The reversal potential is near E = - 60 mV; this current is less specific than the first component.6. In some preparations the delayed current is composed of only one component. This current is activated with a time constant of 0.6 sec at the resting potential and of 1.5 sec at E = - 5 mV. The steady-state value of the degree of activation is 0 at E = - 90 mV and 1 at E = + 30 mV. The reversal potential is between E = - 70 and E = - 60 mV.7. The role of these currents in the processes of repolarization of normal and prolonged action potentials, and in the pace-making activity is discussed.

Action Potentials↗

Voltage-clamp analysis of the early current in frog skeletal muscle fibre using the double sucrose-gap method.

1. The early membrane currents in skeletal muscle fibres have been studied with the double sucrose-gap method, according to the experimental procedure used for the study of the giant axon of the squid.2. The earliest observable current is a capacitative transient. An equivalent circuit with two capacity-resistance systems can account for such a current. The components of the electrical circuit are estimated from the records.3. The capacitative transient current is followed by an initial current, the time and voltage dependence of which are analogous to those of nerve fibres. During this phase of current, the membrane behaves like a sodium electrode for modifications of the external sodium concentration.4. Using tetrodotoxin, a specific inhibitor of the sodium permeability, it is possible to separate two current components, (i) a transient component, suppressed by tetrodotoxin, which reflects the modifications, with time and voltage, of the membrane permeability towards sodium ions; the larger the depolarization, the shorter the time to reach peak current. This current is inward for depolarizations (V) of about +30 mV to about +130 mV (V(Na)). There was some variation in these values between individual fibres. Beyond V(Na), the current is outward. This current shows a small rectification - inward going - for high depolarizations which is comparable to the behaviour of the Ranvier node membrane. (ii) A quasi-instantaneous outward component, only voltage dependent. The current-voltage relation of this current shows an outward going rectification for high depolarizations. This current can be considered as a ;leak' current, in which chloride ions could play an important role.5. A sodium tail current is observed when the imposed potential fall occurs during the time course of the initial current. It corresponds to the deactivation of the sodium current previously activated. Because of the large contemporary capacitative currents, it is difficult to measure accurately its maximum amplitude and its time course: yet, the instantaneous current-voltage relation seems to show a slight rectification for the largest depolarizations, as observed on the Ranvier node membrane.6. The inactivation properties of the sodium current are studied in experiments similar to those described by Hodgkin & Huxley. As in nerve fibres the ability of the membrane to undergo an increase of the sodium permeability depends on the membrane potential. In our experimental conditions, the availability of the sodium carrying system is 90 per cent at the resting potential; the half-inactivation occurs for V = +11 mV. This potential value corresponds to the smallest value of tau(h) (-1), in agreement with the equations proposed by Hodgkin & Huxley (1952d) for the inactivation process.7. The activation parameters (m(infinity), tau(m)) are determined by a fitting method, taking account of the values of tau(h) previously established. The potential of half-activation is near V = +40 mV.

Action Potentials↗