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

Pater, Christine; Sauviat, Martin-Pierre

doi:10.1111/j.1476-5381.1988.tb11549.x

Cited by 7 publications

(4 citation statements)

References 21 publications

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“…Depression of the early plateau in the presence of Cd 2+ is due to the large reduction in the density of I CaL , the main type of Ca 2+ current in rainbow trout cardiac myocytes (Hove-Madsen and Tort 1998; Vornanen 1998). In rainbow trout ventricular myocytes, 10 µM Cd 2+ reduced the peak I CaL density by approximately 85%, which is similar to Cd 2+ -induced reduction of I CaL in cat ventricular myocytes (>95% by 10-20 µM) and frog (Rana esculenta) atrial trabeculae (53% depression by 5 µM Cd 2+ ) (Pater and Sauviat 1988;Wasserstrom and Vites 1999). In rabbit ventricular myocytes, Cd 2+ also inhibits I CaL with high affinity (equilibrium dissociation constant [K d ] of 2.14 µM) (Hobai et al 1997), which agrees well with our results (IC50 = 0.98 µM).…”

Section: Discussionsupporting

confidence: 57%

Cardiac Toxicity of Cadmium Involves Complex Interactions Among Multiple Ion Currents in Rainbow Trout (Oncorhynchus mykiss) Ventricular Myocytes

Haverinen

Badr

Vornanen

2021

Environmental Toxicology and Chemistry

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Cadmium (Cd 2+ ) is cardiotoxic to fish, but its effect on the electrical excitability of cardiac myocytes is largely unknown. To this end, we used the whole-cell patch-clamp method to investigate the effects of Cd 2+ on ventricular action potentials (APs) and major ion currents in rainbow trout (Oncorhynchus mykiss) ventricular myocytes. Trout were acclimated to +4°C, and APs were measured at the acclimated temperature and elevated temperature (+18°C). Cd 2+ (10, 20, and 100 µM) altered the shape of the ventricular AP in a complex manner. The early plateau fell to less positive membrane voltages, and the total duration of AP prolonged. These effects were obvious at both +4°C and +18°C. The depression of the early plateau is due to the strong Cd 2+ -induced inhibition of the L-type calcium (Ca 2+ ) current (I CaL ), whereas the prolongation of the AP is an indirect consequence of the I CaL inhibition: at low voltages of the early plateau, the delayed rectifier potassium (K + ) current (I Kr ) remains small, delaying repolarization of AP. Cd 2+ reduced the density and slowed the kinetics of the Na + current (I Na ) but left the inward rectifier K + current (I K1 ) intact. These altered cellular and molecular functions can explain several Cd 2+ -induced changes in impulse conduction of the fish heart, for example, slowed propagation of the AP in atrial and ventricular myocardia (inhibition of I Na ), delayed relaxation of the ventricle (prolongation of ventricular AP duration), bradycardia, and atrioventricular block (inhibition of I CaL ). These findings indicate that the cardiotoxicity of Cd 2+ in fish involves multiple ion currents that are directly and indirectly altered by Cd 2+ . Through these mechanisms, Cd 2+ may trigger cardiac arrhythmias and impair myocardial contraction. Elevated temperature (+18°C) slightly increases Cd 2+ toxicity in trout ventricular myocytes.

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Section: Discussionsupporting

confidence: 57%

Cardiac Toxicity of Cadmium Involves Complex Interactions Among Multiple Ion Currents in Rainbow Trout (Oncorhynchus mykiss) Ventricular Myocytes

Haverinen

Badr

Vornanen

2021

Environmental Toxicology and Chemistry

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“…However, no T-type Ca channels have yet been observed in frog atrial fibres (Pater & Sauviat, 1988). The third possibility which could account for the shift of I-V curve by PTX is that Ca might accumulate inside the fibre and decrease the potential through the membrane by screening internal negative charges.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

Section: Methodsmentioning

confidence: 99%

“…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.…”

Section: Methodsmentioning

confidence: 99%

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

Sauviat

1989

British J Pharmacology

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1The effect of palytoxin (PTX) on the Ca current (ICa) and the mechanical activity of frog atrial fibres was studied by use of the double sucrose gap voltage clamp technique. 2 In normal Ringer solution, PTX transiently increased the electrically-evoked peak tension which then decreased while a major contracture developed. PTX slowed the time course of the relaxation phase of the evoked tension. 3 Evidence is presented which suggests that the toxin also increased the entry of Ca and Sr via the Na-Ca exchange mechanism. It also induced the development of a Ca-dependent outward current which was inhibited by Sr. 4 In Na-free solution, PTX increased ICa and shifted the reversal potential for Ca towards more negative membrane potentials, thus suggesting that the internal Ca concentration had increased. Current-voltage, tension-voltage, time to peak-voltage and inactivation time constant-membrane potential curves were all shifted towards more negative membrane potentials in the presence of PTX. 5 These effects of PTX are similar to those caused by the increase in internal Ca concentration induced by Na ionophores by way of voltage-dependent Ca influx of the Na-Ca exchange mechanism.

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Palytoxin increases an outward K+ current in frog heart fibres

Sauviat

1989

Pflugers Arch.

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

Abstract: 1 The effect of cadmium (Cd) on the slow inward current (Ij)

Cited by 7 publications

References 21 publications

Cardiac Toxicity of Cadmium Involves Complex Interactions Among Multiple Ion Currents in Rainbow Trout (Oncorhynchus mykiss) Ventricular Myocytes

Cardiac Toxicity of Cadmium Involves Complex Interactions Among Multiple Ion Currents in Rainbow Trout (Oncorhynchus mykiss) Ventricular Myocytes

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

Palytoxin increases an outward K+ current in frog heart fibres

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