Electrophysiological effects of diclofurime on rabbit and frog atrial heart muscle

Abstract

1The effects of diclofurime on the electrical activity of the rabbit sinus node, rabbit atria and frog atrial fibres were studied using microelectrode and the double sucrose gap voltage-clamp techniques respectively. 2 In rabbit sinus node, diclofurime (l0-7 M to 10-6 M) decreased the action potential (AP) amplitude and maximum rate of depolarization ( V.J, increased the AP duration and slowed the sinus rate.3 In rabbit atria, the drug reduced the amplitude of the depolarizing phase and tx, lengthened the AP duration and decreased the resting membrane potential. 4 In frog atrial fibres, the drug (10-' M) depolarized the resting membrane potential, decreased , as well as the plateau amplitude. It inhibited the sodium current (INa) with a dissociation constant of 3.7 x I o-0 M and a one to one relationship between the drug molecule and the Na channel. Diclofurime did not alter the apparent reversal potential for the fast Na current (ENa) but it inhibited the sodium conductance (GNa) in a frequency-dependent manner.

Effects of cadmium on the slow inward current of frog heart muscle in relation to a lowering of pH in external solution

“…In the present study, the effect of Cd (used as CdCI2) on the slow conductance was studied. Thus, the Ringer control solution contained tetrodotoxin (TTX, 0.57 pM) at a concentration that inhibits Na conductance (Sauviat, 1981) and 1 mm Cd was added to the control solution to block completely ISj (Gautier et al, 1987). In all experiments, measurements were made when the preparations reached an apparent steady-state, that is after 1 min in test solution.…”

“…In current-voltage relationships (I-V curves), outward current corresponds to positive current and depolarizations to positive potentials applied from HP. The apparent reversal potentials (Erey) for Ij were determined as the intersection of the positive slope of I-V curves drawn in the absence and in the presence of the studied cation in the control solution and after total blockade of the current by the appropriate inhibitor (Gautier et al, 1987). According to Horackova & Vassort (1979), the double sucrose gap technique does not seriously affect the measurement of either slow inward current or tension, or the accuracy of voltage-tensioncurrent relationships since only a very small deviation (a few mV) of the intracellularly recorded potential from the applied clamp potential occurred during the initial 5 to lOms of the imposed clamp.…”

“…Diverse accounts of the toxic action of cadmium (Cd) in the cardiovascular (Williams et al, 1978;Kopp et al, 1982;Kopp, 1986) and in the central nervous system (Arvidson, 1981) have been given. Cd ions have been found to be a selective blocker of the slow inward current (Is;) in various species (Kostyuk et al, 1977;Lee & Tsien, 1982; Giles et al, 1983;Josephson et al, 1984;Gautier et al, 1987). In addition, H ions, known to depress ISi in heart muscle (Chesnais et al, 1975), have also been found to cause a dramatic enhancement of the negative inotropic effect of Cd in frog cardiac muscle mechanical activity (Horiuchi & Hayashi, 1979).…”

Effect of palytoxin on the calcium current and the mechanical activity of frog heart muscle

“…Current (clamp) and voltage clamp experiments were performed at 5-80C on fine atrial trabeculae (75-150pm in diameter, 2-4mm in length) isolated from the heart of Rana esculenta using the double sucrose gap technique with vaseline seals (Rougier et al, 1968). The limitation of the voltage clamp method, as applied to a multicellular preparation, as well as the experimental procedure have been discussed previously (Sauviat, 1980;Sauviat & Suchaud, 1981;Sauviat et al, 1987;Gautier et al, 1987;Pater & Sauviat, 1988). Starting from the holding potential, the potential of the test node was displaced in rectangular steps at a rate of 0.2 Hz; positive potentials correspond to depolarization.…”

“…I-V curves were successively drawn for peak ICa in (i) the control solution; (ii) PTX; (iii) PTX and Cd (1 mM). Since 1 mM Cd inhibits ICa, the point of intersection of I-V curves drawn in the absence and in the presence of Cd corresponds to Vc, (Gautier et al, 1987;Pater & Sauviat, 1988). Mechanical activity was recorded by means of a transducer system (Pixie 8101) applied to the fibre by means of a thin glass lever under two experimental conditions.…”