Influence of long-chain acylcarnitines on voltage-dependent calcium current in adult ventricular myocytes.
Long-chain acylcarnitines (LCAC) increase 3.5-fold within 2 min in ischemic myocardium in vivo, and previous studies have suggested, through indirect evidence, that LCAC can stimulate the voltage-dependent L-type Ca2+ current [ICa(L)] in both cardiac and smooth muscle cells. In the present study, whole cell voltage-clamp procedures were performed in isolated adult guinea pig ventricular myocytes to assess the direct effect of LCAC on ICa(L). The intracellular solution contained (in mM) 80 CsCl, 40 K-aspartic acid, and 5 ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA). Maximal current density of ICa(L) at 0 mV was 10.1 +/- 0.5 pA/pF (n = 22) at extracellular Ca2+ concentration ([Ca2+]o) = 2.7 mM. LCAC induced a concentration (1-25 microM, n = 23)- and time-dependent, reversible decrease in ICa(L). When delivered extracellularly for 10 min, LCAC (5 microM) inhibited the maximal current of ICa(L) by 48.1 +/- 1.3% (n = 9, P less than 0.01) and shifted the half-maximal voltage of steady-state activation and inactivation from -13.1 +/- 0.5 to -6.8 +/- 0.4 mV (n = 4; P less than 0.05) and from -21.8 +/- 0.2 to -16.5 +/- 0.6 mV (n = 4; P less than 0.01), respectively. Intracellular delivery of LCAC (5 microM) also suppressed ICa(L) to a similar degree (47.5 +/- 1.5%, n = 4; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Wu
J
J
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
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D000818:Animals; D001682:Biological Availability; D002118:Calcium / Q000502:physiology*; D002331:Carnitine / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D006352:Heart Ventricles; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000166:cytology; D009994:Osmolar Concentration; D013997:Time Factors
D002331:Carnitine; D002118:Calcium