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

Abstract

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.

Palytoxin disrupts cardiac excitation-contraction coupling through interactions with P-type ion pumps

“…2-4). These alterations of atrial [Ca 2ϩ ] i signaling may well explain the negative inotropic and arrhythmogenic effects of palytoxin noted in earlier studies (23,38,41). Further examination of the subcellular patterns of Ca 2ϩ signaling revealed spatial inhomogeneities in the palytoxin effects and identified spontaneous release of Ca 2ϩ , predominantly from the subsarcolemmal j-SR, as the underlying mechanism for the Because palytoxin seriously impairs atrial Ca 2ϩ signaling, it follows that the mechanism of CICR is somehow affected by the toxin, either directly or indirectly.…”

“…Further examination of the subcellular patterns of Ca 2ϩ signaling revealed spatial inhomogeneities in the palytoxin effects and identified spontaneous release of Ca 2ϩ , predominantly from the subsarcolemmal j-SR, as the underlying mechanism for the Because palytoxin seriously impairs atrial Ca 2ϩ signaling, it follows that the mechanism of CICR is somehow affected by the toxin, either directly or indirectly. Previous voltage clamp studies of atrial trabeculae and isolated ventricular myocytes found palytoxin-mediated changes of I Ca (27,41). In both cases, however, these changes were attributed to secondary effects caused mainly by a shift of the reversal potential of I Ca due to intracellular Ca 2ϩ accumulation.…”

“…In addition, palytoxin exerts direct effects on the heart, including depolarization of resting membrane potential, changes of action potential (AP) configuration, generation of afterpotentials and arrhythmias, reduction of phasic tension, and contracture (23,24,38,41,42,51). Studies of the underlying mechanisms, however, are sparse and controversial (11,12,41,42). Given the pronounced effects on ion homeostasis, membrane potential, and tension, palytoxin is expected to markedly alter cardiac excitation-contraction (E-C) coupling.…”

Scientific Opinion on marine biotoxins in shellfish - Palytoxin group

“…In addition to Na + , K + -ATPase, other plasma membrane components involved in transport of other ions have been proposed to contribute to molecular responses induced by PlTX (Muramatsu et al, 1984;Ikeda et al, 1988;Sauviat, 1989;Frelin and Van Renterghem, 1995;Vale et al, 2006), but the existence of PlTX targets other than the Na + , K + -ATPase is uncertain (Tosteson, 2000).…”

NO Metabolites Levels in Human Red Blood Cells are Affected by Palytoxin, an Inhibitor of Na+/K+-ATPase Pump

“…Extremely low concentrations of PTX, following its binding to Na + /K + ATPase, is able to depolarize the cell by inducing a lower conductance and the appearance of relatively non-selective cation channels which likely include, at least, part of the pump’s ion translocation pathway [ 4 - 7 ]. Altered ionic homeostasis, induced by PTX, influences other equilibria such as those of Ca 2+ and H + ions, inducing a collapse of the mechanisms controlling the ion-water balance, resulting ultimately for several cellular effects [ 5 , 8 , 9 ]. Na + /K + ATPase, as shown by data obtained with oubain, represents the main binding site for PTX [ 10 ].…”