Palytoxin acidifies chick cardiac cells and activates the Na<sup>+</sup>/H<sup>+</sup> antiporter

Frelin, Christian; Vigne, Paul; Breittmayer, Jean‐Philippe

doi:10.1016/0014-5793(90)80765-b

Cited by 26 publications

(12 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent attention has been given to the action of various amiloride derivatives on PTX actions. In chick cardiomyocytes, PTX increases the permeability to H+, thereby leading to an intracellular acidification, and to a secondary activation of the Na+/H+ antiporter (Frelin et al, 1990b). As a consequence, part of the PTX-activated 22Na' flux component could be inhibited by ethylisopropylamiloride (Frelin et al, 1990b).…”

Section: Introductionmentioning

confidence: 99%

“…In chick cardiomyocytes, PTX increases the permeability to H+, thereby leading to an intracellular acidification, and to a secondary activation of the Na+/H+ antiporter (Frelin et al, 1990b). As a consequence, part of the PTX-activated 22Na' flux component could be inhibited by ethylisopropylamiloride (Frelin et al, 1990b). The remaining PTX-activated 22Na' flux is blocked by 3,4 dichlorobenzamil, another derivative of amiloride that is well known to block the Na+/Ca2+ exchange activity (Frelin et al, 1990a).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

3,4 Dichlorobenzamil‐sensitive, monovalent cation channel induced by palytoxin in cultured aortic myocytes

Renterghem

Frelin

1993

British J Pharmacology

Self Cite

View full text Add to dashboard Cite

1 Smooth muscle cells were dispersed from rat aorta and then cultured. The action of palytoxin on rat aortic myocytes was analysed by measurement of 22Na+ uptake and single channel recording techniques. 2 Palytoxin induced an increase in 22Na+ uptake, with a concentration of 50 nM producing halfmaximal activation. The action of palytoxin was inhibited by amiloride derivatives and by ouabain. The concentrations of inhibitor producing half-maximal inhibition were 10 JIM for 3,4 dichlorobenzamil, 30 JAM for benzamil, 100 JAM for phenamil and 1 mm for ouabain. 3 In outside-out patches, palytoxin induced single channel currents that reversed near 0 mV with NaCl or KCI in the extracellular solution, but were outward with N-methyl-D-glucamine chloride or CaCl2 ( 10 mM), indicating that palytoxin induced a cation channel permeable to Na+ and K+ (PK/PNa = 1.2) but not to Ca2+ (PK/PCa > 30) or to N-methyl-D-glucamine (NMDG) (PK/PNMDG> 11). The unit channel conductance was 11 -14 pS. 4 A high (>0.1 mM) extracellular concentration of Ca2+ was necessary to observe channel activation by palytoxin. A high (150 mM) extracellular concentration of K+ partially prevented and reversed channel activation by palytoxin. 5 The channel activity was fully blocked by 3,4 dichlorobenzamil (20 JAM) and partially blocked by phenamil (50 JM). It was not reduced by ouabain (200 JAM).

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

3,4 Dichlorobenzamil‐sensitive, monovalent cation channel induced by palytoxin in cultured aortic myocytes

Renterghem

Frelin

1993

British J Pharmacology

Self Cite

View full text Add to dashboard Cite

show abstract

“…PTX has also been shown to open an H + conductive pathway with a resulting activation of Na + /H + exchanger in bovine adrenal chromaffin cells [23]. This was shown to result in cardiac cellular acidification in embryonic chick ventricular cells [8].…”

Section: Discussionmentioning

confidence: 98%

“…PTX is the suspected agent in Haff disease, in which rhabdomyolysis occurs within 24 h of eating contaminated fish such as buffalo fish. PTX is primarily present in soft corals or in dinoflagellates, and it can contaminate crustaceans and other fish as it bioaccumulates up the food chain [8]. Only 23 cases have been reported in the USA, including two recent cases in New York City [9].…”

Section: Introductionmentioning

confidence: 99%

Case Series: Inhaled Coral Vapor—Toxicity in a Tank

Sud

Greller

et al. 2013

J. Med. Toxicol.

View full text Add to dashboard Cite

“…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.…”

mentioning

confidence: 99%

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

Kockskämper

Ahmmed²,

Zima³

et al. 2004

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

Palytoxin is a coral toxin that seriously impairs heart function, but its effects on excitation-contraction (E-C) coupling have remained elusive. Therefore, we studied the effects of palytoxin on mechanisms involved in atrial E-C coupling. In field-stimulated cat atrial myocytes, palytoxin caused elevation of diastolic intracellular Ca 2ϩ concentration ([Ca 2ϩ ]i), a decrease in [Ca 2ϩ ]i transient amplitude, Ca 2ϩ alternans followed by [Ca 2ϩ ]i waves, and failures of Ca 2ϩ release. The decrease in [Ca 2ϩ ]i transient amplitude occurred despite high sarcoplasmic reticulum (SR) Ca 2ϩ load. In voltage-clamped myocytes, palytoxin induced a current with a linear current-voltage relationship (reversal potential ϳ5 mV) that was blocked by ouabain. Whole cell Ca 2ϩ current and ryanodine receptor Ca 2ϩ release channel function remained unaffected by the toxin. However, palytoxin significantly reduced Ca 2ϩ pumping of isolated SR vesicles. In currentclamped myocytes stimulated at 1 Hz, palytoxin induced a depolarization of the resting membrane potential that was accompanied by delayed afterdepolarizations. No major changes of action potential configuration were observed. The results demonstrate that palytoxin interferes with the function of the sarcolemmal Na ϩ -K ϩ pump and the SR Ca 2ϩ pump. The suggested mode of palytoxin toxicity in the atrium involves the conversion of Na ϩ -K ϩ pumps into nonselective cation channels as a primary event followed by depolarization, Na ϩ accumulation, and Ca 2ϩ overload, which, in turn, causes arrhythmogenic [Ca 2ϩ ]i waves and delayed afterdepolarizations. atrial myocytes; intracellular calcium PALYTOXIN IS A NONPEPTIDE TOXIN with a unique chemical structure isolated from corals of the genus Palythoa (34). It is the most potent animal toxin known to date (14, 50). Palytoxin intoxication leads to severe vasoconstriction, depression of cardiac function (25, 50), and, possibly, myocardial damage (36). At the cellular level, the toxin causes Na ϩ influx and K ϩ efflux, accompanied by depolarization, in all mammalian cell types studied (14). Cardiac glycosides (cymarin, ouabain, and digitoxin), specific inhibitors of the Na ϩ -K ϩ pump (Na ϩ -K ϩ -ATPase), can partially or fully antagonize the actions of palytoxin, pointing to the Na ϩ -K ϩ pump as the molecular target of the toxin (14). Nevertheless, several other modes of action have been proposed (10). Recent studies of yeast cells expressing mammalian Na ϩ -K ϩ pumps (39, 46) and of isolated Na ϩ -K ϩ pumps incorporated into planar lipid bilayers (18, 26), however, have shown unambiguously that palytoxin indeed targets the Na ϩ -K ϩ pump, converting the enzyme into a nonselective cation channel (summarized in Ref. 44). Furthermore, elegant kinetic studies of palytoxin-induced channels in cardiac myocytes and HEK-293 cells strongly support the notion that the toxin binds to the pump molecule and locks it in a channel-like open state (2).In the heart, palytoxin leads to myocardial ischemia, ventricular fibrillation, and cardiac fa...

show abstract

Palytoxin acidifies chick cardiac cells and activates the Na⁺/H⁺ antiporter

Cited by 26 publications

References 26 publications

3,4 Dichlorobenzamil‐sensitive, monovalent cation channel induced by palytoxin in cultured aortic myocytes

3,4 Dichlorobenzamil‐sensitive, monovalent cation channel induced by palytoxin in cultured aortic myocytes

Case Series: Inhaled Coral Vapor—Toxicity in a Tank

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

Contact Info

Product

Resources

About

Palytoxin acidifies chick cardiac cells and activates the Na+/H+ antiporter

Cited by 26 publications

References 26 publications

3,4 Dichlorobenzamil‐sensitive, monovalent cation channel induced by palytoxin in cultured aortic myocytes

3,4 Dichlorobenzamil‐sensitive, monovalent cation channel induced by palytoxin in cultured aortic myocytes

Case Series: Inhaled Coral Vapor—Toxicity in a Tank

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

Contact Info

Product

Resources

About

Palytoxin acidifies chick cardiac cells and activates the Na⁺/H⁺ antiporter