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

• Published in: American Journal of Physiology: Cell Physiology Vol. 56; no. 2; pp. C527 - C538
• Main Authors: KOCKSKÄMPER, Jens, AHMMED, Gias U, ZIMA, Aleksey V, SHEEHAN, Katherine A, GLITSCH, Helfried G, BLATTER, Lothar A
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Physiological Society 01.08.2004
• Subjects: Biological and medical sciences; Cell physiology; Cells; Fundamental and applied biological sciences. Psychology; Heart; Ions; Molecular and cellular biology; Muscle contraction; Toxins; Vertebrates: cardiovascular system; Heart; Fissipedia; Carnivora; Load; Palytoxin; Calcium; Excitation contraction coupling; Enzyme; atrial myocytes; Ryanodine receptor; Electrophysiology; Ion transport; transporting ATPase; Myocyte; Toxin; Vertebrata; Mammalia; Sarcoplasmic reticulum; Cat; Hydrolases; intracellular calcium; Circulatory system; Ca; Release
• ISSN: 0363-6143; 1522-1563

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 Ca2+ concentration ([Ca2+]i), a decrease in [Ca2+]i transient amplitude, Ca2+ alternans followed by [Ca2+]i waves, and failures of Ca2+ release. The decrease in [Ca2+]i transient amplitude occurred despite high sarcoplasmic reticulum (SR) Ca2+ load. In voltage-clamped myocytes, palytoxin induced a current with a linear current-voltage relationship (reversal potential 5 mV) that was blocked by ouabain. Whole cell Ca2+ current and ryanodine receptor Ca2+ release channel function remained unaffected by the toxin. However, palytoxin significantly reduced Ca2+ pumping of isolated SR vesicles. In current-clamped 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+-K+ pump and the SR Ca2+ pump. The suggested mode of palytoxin toxicity in the atrium involves the conversion of Na+-K+ pumps into nonselective cation channels as a primary event followed by depolarization, Na+ accumulation, and Ca2+ overload, which, in turn, causes arrhythmogenic [Ca2+]i waves and delayed afterdepolarizations. [PUBLICATION ABSTRACT]