PALMITOYL CARNITINE MODIFIES SODIUM CURRENTS AND INDUCES TRANSIENT INWARD CURRENT IN VENTRICULAR MYOCYTES

Long-chain acylcarnitines increase within 2 min in ischemic myocardium in vivo and induce delayed afterdepolarizations (DADs) and complex os cillations of membrane potential in vitro. This study was performed to assess the ionic currents underlying these electrophysiological alter ations in isolated rabbit ventricular cells using whole cell voltage-c lamp procedures. Palmitoyl carnitine (10 mu M, for 6-10 min) elicited a transient inward current (I-ti) in the presence of blockade of Ca2and K+ channels. The effect of palmitoyl carnitine was reversible afte r washout (n = 6). The amplitude of I-ti was dependent on the amplitud e of the preceding depolarization step. Palmitoyl carnitine (10 mu M, for > 2 min) also induced another inward current, which was activated spontaneously at potentials between -120 and -20 mV with a linear curr ent-voltage relationship (1.0 +/- 0.1 nA at -80 mV). This current was abolished by replacing extracellular Na+ with tetraethylammonium chlor ide, indicating that Na+ was the charge carrier. Inactivation of this current was slow (gamma = 885.9 +/- 89.1 ms, n = 12) or incomplete, in dicating the appearance of a slow-inactivating Naf inward current [I-N a(s)]. Palmitoyl carnitine always induced I-Na(s) before the appearanc e of I-ti. Intracellular ethylene glycol-bis(beta-aminoethyl ether)-N, N,N',N'-tetraacetic acid (10 mM) abolished I-ti but did not suppress I -Na(s) (n = 4), indicating that I-Na(s) was not activated by intracell ular Ca2+ (Ca-i(2+)). Tetrodotoxin (10 mu M) also decreased the amplit ude of I-Na(s). Thus palmitoyl carnitine induces I-Na(s), which likely leads to an increase in Na+ influx, thereby eliciting an increase in Ca-i(2+) via the Na+-Ca2+ exchanger and leading to the development of I-ti, DADs, and triggered activity.