HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 287/2/C527    most recent 00541.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Kockskämper, J. Articles by Blatter, L. A. Search for Related Content PubMed PubMed Citation Articles by Kockskämper, J. Articles by Blatter, L. A.

MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

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

¹Department of Physiology, Loyola University Chicago, Maywood, Illinois 60153; and ²Arbeitsgruppe Muskelphysiologie, Fakultät für Biologie, Ruhr-Universität, D-44780 Bochum, Germany

Submitted 4 December 2003 ; accepted in final form 5 April 2004

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.

atrial myocytes; intracellular calcium

This article has been cited by other articles:

				Y.-C. Wang and R.-C. Huang Effects of Sodium Pump Activity on Spontaneous Firing in Neurons of the Rat Suprachiasmatic Nucleus J Neurophysiol, July 1, 2006; 96(1): 109 - 118. [Abstract] [Full Text] [PDF]

				G. R. Dubyak Ion homeostasis, channels, and transporters: an update on cellular mechanisms Advan Physiol Educ, December 1, 2004; 28(4): 143 - 154. [Abstract] [Full Text] [PDF]