Free, long-chain, polyunsaturated fatty acids reduce membrane electrical excitability in neonatal rat cardiac myocytes.
Because previous studies showed that polyunsaturated fatty acids can reduce the contraction rate of spontaneously beating heart cells and have antiarrhythmic effects, we examined the effects of the fatty acids on the electrophysiology of the cardiac cycle in isolated neonatal rat cardiac myocytes. Exposure of cardiomyocytes to 10 microM eicosapentaenoic acid for 2-5 min markedly increased the strength of the depolarizing current required to elicit an action potential (from 18.0 +/- 2.4 pA to 26.8 +/- 2.7 pA, P < 0.01) and the cycle length of excitability (from 525 ms to 1225 ms, delta = 700 +/- 212, P < 0.05). These changes were due to an increase in the threshold for action potential (from -52 mV to -43 mV, delta = 9 +/- 3, P < 0.05) and a more negative resting membrane potential (from -52 mV to -57 mV, delta = 5 +/- 1, P < 0.05). There was a progressive prolongation of intervals between spontaneous action potentials and a slowed rate of phase 4 depolarization. Other polyunsaturated fatty acids--including docosahexaenoic acid, linolenic acid, linoleic acid, arachidonic acid, and its nonmetabolizable analog eicosatetraynoic acid, but neither the monounsaturated oleic acid nor the saturated stearic acid--had similar effects. The effects of the fatty acids could be reversed by washing with fatty acid-free bovine serum albumin. These results show that free polyunsaturated fatty acids can reduce membrane electrical excitability of heart cells and provide an electrophysiological basis for the antiarrhythmic effects of these fatty acids.
Kang
J X
JX
Department of Medicine, Harvard Medical School, Boston, MA, USA.
Xiao
Y F
YF
Leaf
A
A
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D000831:Animals, Newborn; D016718:Arachidonic Acid / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006321:Heart / Q000502:physiology*; D007700:Kinetics; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D051381:Rats; D013329:Structure-Activity Relationship; D013997:Time Factors; D017962:alpha-Linolenic Acid / Q000494:pharmacology
D005230:Fatty Acids, Nonesterified; D005231:Fatty Acids, Unsaturated; D008041:Linoleic Acids; D017962:alpha-Linolenic Acid; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D019787:Linoleic Acid; D015118:Eicosapentaenoic Acid