Enhanced suppression of myocardial slow action potentials during hypoxia by free fatty acids.
Effects of free fatty acids (palmitate and linoleate) on myocardial contractility and slow action potentials (APs) were examined in Langendorff-perfused chick hearts. To study the slow APs exclusively, the fast Na+ channels were voltage-inactivated in elevated K+ (25 mM), and the concentration of Ca2+ ion was increased to 5.4 mM in order to induce slow APs. Palmitate (0.18, 0.54 or 0.72 mM) along with albumin (0.12 mM) was added to the perfusate. Albumin by itself did not affect contractility or the slow APs during normoxia and hypoxia. Under well oxygenated conditions, palmitate had no effect on contractility or the slow APs. However, palmitate accelerated the decline of contractility during hypoxia in a dose-dependent fashion. Hypoxia suppressed the slow APs, and palmitate and linoleate further exacerbated the suppression of slow APs produced by hypoxia. Nevertheless, palmitate and linoleate did not enhance the hypoxic reduction of the tissue high energy phosphate level. The present results suggest that free fatty acids elicit cardio-depressant effects on hearts through their direct action on the myocardial cell membrane (slow channels) rather than through any metabolic effects.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002645:Chickens; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D004573:Electrolytes / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D000860:Hypoxia / Q000503:physiopathology*; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000494:pharmacology
D004573:Electrolytes; D005230:Fatty Acids, Nonesterified; D008041:Linoleic Acids; D010169:Palmitic Acids; D019308:Palmitic Acid; D000255:Adenosine Triphosphate; D019787:Linoleic Acid