title: Effects of arrhythmogenic lipid metabolites on the L-type calcium current of diabetic vs. non-diabetic rat hearts.
abstract: Accumulation of lipid metabolites, such as palmitoylcarnitine and lysophosphatidylcholine, is thought to be a major contributor to the development of cardiac arrhythmias during myocardial ischemia. This arrhythmogenicity is likely due to the effects of these metabolites on various ion channels. Diabetic hearts have been shown to accumulate much higher concentrations of these lipid metabolites during ischemia, which may be an important factor in the enhanced incidence of arrhythmias in diabetic hearts. However, it is not known whether these metabolites have similar effects on the ion channels of diabetic hearts as in non-diabetic hearts. Previous studies on myocytes from non-diabetic hearts have reported either enhancement or inhibition of L-type calcium current (I(Ca)) by these lipid metabolites. Thus, it is not clear whether the effects of palmitoylcarnitine and/or lysophosphatidlycholine on I(Ca) contribute to the enhanced arrhythmogenicity of diabetic hearts or protect against arrhythmias. We determined the effect of exogenous palmitoylcarnitine and lysophosphatidylcholine on the (I(Ca)) in ventricular myocytes from streptozotocin-diabetic and non-diabetic rat hearts under identical conditions. We found that palmitoylcarnitine and lysophosphatidylcholine exhibited a dose-dependent inhibition of I(Ca), which was virtually identical in diabetic and non-diabetic cardiac myocytes. Thus, we conclude that these arrhythmogenic lipid metabolites have similar actions on calcium channels in diabetic and non-diabetic hearts. Therefore, the greater susceptibility of diabetic hearts to arrhythmias during myocardial ischemia is not due to an altered sensitivity of the L-type calcium channels to lipid metabolites, but may be explained, in large part, by the greater accumulation of these metabolites during ischemia.
authors.affiliation: Department of Physiology, Midwestern University, Downers Grove, IL 60515, USA.
authors.forename: M T
authors.initials: MT
authors.lastname: Ziolo
authors.forename: K L
authors.initials: KL
authors.lastname: Sondgeroth
authors.forename: C H
authors.initials: CH
authors.lastname: Harshbarger
authors.forename: J M
authors.initials: JM
authors.lastname: Smith
authors.forename: G M
authors.initials: GM
authors.lastname: Wahler
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D007511:Ischemia / Q000378:metabolism; D050356:Lipid Metabolism; D008244:Lysophosphatidylcholines / Q000737:chemistry / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010172:Palmitoylcarnitine / Q000737:chemistry / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D013997:Time Factors
chemical_list: D020746:Calcium Channels, L-Type; D008244:Lysophosphatidylcholines; D010172:Palmitoylcarnitine; D002118:Calcium