K+ current inhibition by amphiphilic fatty acid metabolites in rat ventricular myocytes

被引:28
作者
Xu, Z [1 ]
Rozanski, GJ [1 ]
机构
[1] Univ Nebraska, Coll Med, Dept Physiol & Biophys, Med Ctr, Omaha, NE 68198 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 1998年 / 275卷 / 06期
关键词
heart; potassium channels; fatty acids; transient outward current;
D O I
10.1152/ajpcell.1998.275.6.C1660
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Fatty acid metabolites accumulate in the heart under pathophysiological conditions that affect beta-oxidation and can elicit marked electrophysiological changes that are arrhythmogenic. The purpose of the present study was to determine the impact of amphiphilic fatty acid metabolites on K+ currents that control cardiac refractoriness and excitability. Transient outward (I-to) and inward rectifier (I-K1) K+ currents were recorded by the whole cell voltage-clamp technique in rat ventricular myocytes, and the effects of two major fatty acid metabolites were examined: palmitoylcarnitine and palmitoyl-coenzyme A (palmitoyl-CoA). Palmitoylcarnitine (0.5-10 mu M) caused a concentration-dependent decrease in I-to density in myocytes internally dialyzed with the amphiphile; 10 mu M reduced mean I-to density at +60 mV by 62% compared with control (P < 0.05). In contrast, external palmitoylcarnitine at the same concentrations had no effect, nor did internal dialysis significantly alter I-K1 Dialysis with palmitoyl-CoA (1-10 mu M) produced a smaller decrease in I-to density compared with that produced by palmitoylcarnitine; 10 mu M reduced mean L density at +60 mV by 37% compared with control (P < 0.05). Both metabolites delayed recovery of I-to from inactivation but did not affect voltage-dependent properties. Moreover, the effects of palmitoylcarnitine were relatively specific, as neither palmitate (10 mu M) nor carnitine (10 mu M) alone significantly influenced I-to when added to the pipette solution. These data therefore suggest that amphiphilic fatty acid metabolites downregulate I-to channels by a mechanism confined to the cytoplasmic side of the membrane. This decrease in cardiac K+ channel activity may delay repolarization under pathophysiological conditions in which amphiphile accumulation is postulated to occur, such as diabetes mellitus or myocardial infarction.
引用
收藏
页码:C1660 / C1667
页数:8
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