Uncoupling of cardiac cells by fatty acids: structure-activity relationships.
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.
Burt
J M
JM
Department of Physiology, University of Arizona, Tucson 85724.
Massey
K D
KD
Minnich
B N
BN
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004553:Electric Conductivity; D005229:Fatty Acids, Monounsaturated; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D005233:Fatty Alcohols / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology; D010169:Palmitic Acids / Q000494:pharmacology; D051381:Rats; D013229:Stearic Acids / Q000494:pharmacology; D013329:Structure-Activity Relationship
D005229:Fatty Acids, Monounsaturated; D005230:Fatty Acids, Nonesterified; D005233:Fatty Alcohols; D009829:Oleic Acids; D010169:Palmitic Acids; D013229:Stearic Acids; C008757:palmitoleic acid; D019301:Oleic Acid; C031183:stearic acid