AJP - Cell Physiology, Vol 260, Issue 3 C439-C448, Copyright © 1991 by American Physiological Society

ARTICLES

Uncoupling of cardiac cells by fatty acids: structure-activity relationships

J. M. Burt, K. D. Massey and B. N. Minnich
Department of Physiology, University of Arizona, Tucson 85724.

The permeability and conductance of gap junctions between pairs of neonatal rat heart cells were rapidly and reversibly decreased by oleic acid in a dose- and time-dependent manner. Other unsaturated fatty acids (C-18: cis 6, 9, or 11, and C-18, 16, and 14, cis 9), saturated fatty acids (C-10, 12, and 14), and saturated fatty alcohols (C-8, 10, and 12) also caused uncoupling. The most effective compounds of the unsaturated and saturated fatty acid and saturated fatty alcohol series caused essentially complete uncoupling at comparable aqueous concentrations. However, oleic acid uncoupled cells at membrane concentrations as low as 1 mol%, whereas decanoic acid required upwards of 35 mol%. The channels that support the action potential remained functional at these same membrane concentrations. The data are discussed in terms of the possible mechanism by which these compounds cause uncoupling and the possible role of uncoupling by nonesterified free fatty acids in the initiation of arrhythmias during and after ischemic insults.

This article has been cited by other articles:

				A. Rodriguez-Sinovas, D. Garcia-Dorado, M. Ruiz-Meana, and J. Soler-Soler Protective effect of gap junction uncouplers given during hypoxia against reoxygenation injury in isolated rat hearts Am J Physiol Heart Circ Physiol, February 1, 2006; 290(2): H648 - H656. [Abstract] [Full Text] [PDF]

				M. Radisic, L. Yang, J. Boublik, R. J. Cohen, R. Langer, L. E. Freed, and G. Vunjak-Novakovic Medium perfusion enables engineering of compact and contractile cardiac tissue Am J Physiol Heart Circ Physiol, February 1, 2004; 286(2): H507 - H516. [Abstract] [Full Text] [PDF]

				A. Arutunyan, A. Pumir, V. Krinsky, L. Swift, and N. Sarvazyan Behavior of ectopic surface: effects of {beta}-adrenergic stimulation and uncoupling Am J Physiol Heart Circ Physiol, December 1, 2003; 285(6): H2531 - H2542. [Abstract] [Full Text] [PDF]

				A. Arutunyan, L. M. Swift, and N. Sarvazyan Initiation and propagation of ectopic waves: insights from an in vitro model of ischemia-reperfusion injury Am J Physiol Heart Circ Physiol, August 1, 2002; 283(2): H741 - H749. [Abstract] [Full Text] [PDF]

				X. Qi, P. Varma, D. Newman, and P. Dorian Gap Junction Blockers Decrease Defibrillation Thresholds Without Changes in Ventricular Refractoriness in Isolated Rabbit Hearts Circulation, September 25, 2001; 104(13): 1544 - 1549. [Abstract] [Full Text] [PDF]

				A. Arutunyan, D. R. Webster, L. M. Swift, and N. Sarvazyan Localized injury in cardiomyocyte network: a new experimental model of ischemia-reperfusion arrhythmias Am J Physiol Heart Circ Physiol, April 1, 2001; 280(4): H1905 - H1915. [Abstract] [Full Text] [PDF]

				T. J. Avis and R. R. Bélanger Specificity and Mode of Action of the Antifungal Fatty Acid cis-9-Heptadecenoic Acid Produced by Pseudozyma flocculosa Appl. Envir. Microbiol., February 1, 2001; 67(2): 956 - 960. [Abstract] [Full Text]

				D. S. He and J. M. Burt Mechanism and Selectivity of the Effects of Halothane on Gap Junction Channel Function Circ. Res., June 9, 2000; 86 (11): e104 - e109. [Abstract] [Full Text] [PDF]

				E. Carmeliet Cardiac Ionic Currents and Acute Ischemia: From Channels to Arrhythmias Physiol Rev, July 1, 1999; 79(3): 917 - 1017. [Abstract] [Full Text] [PDF]

				G. J. Christ, M. Spektor, P. R. Brink, and L. Barr Further evidence for the selective disruption of intercellular communication by heptanol Am J Physiol Heart Circ Physiol, June 1, 1999; 276(6): H1911 - H1917. [Abstract] [Full Text] [PDF]

				K. L. MacDonell, D. L. Severson, and W. R. Giles Depression of excitability by sphingosine 1-phosphate in rat ventricular myocytes Am J Physiol Heart Circ Physiol, December 1, 1998; 275(6): H2291 - H2299. [Abstract] [Full Text] [PDF]

				S. Rohr, J. P. Kucera, and A. G. Kleber Slow Conduction in Cardiac Tissue, I : Effects of a Reduction of Excitability Versus a Reduction of Electrical Coupling on Microconduction Circ. Res., October 19, 1998; 83(8): 781 - 794. [Abstract] [Full Text] [PDF]

				D. L. Boger, J. E. Patterson, X. Guan, B. F. Cravatt, R. A. Lerner, and N. B. Gilula Chemical requirements for inhibition of gap junction communication by the biologically active lipid oleamide PNAS, April 28, 1998; 95(9): 4810 - 4815. [Abstract] [Full Text] [PDF]