Abstract
We investigated the effects of ischemia-related amphipathic compounds, palmitoylcarnitine (PamCar, 0.5–50 μM) and lysophosphatidylcholine (lysoPtdCho, 5–50 μM) on sodium current (I Na) of guinea-pig ventricular myocytes. The cells were perfused with low-Na+ (60 mM) Tyrode's solution, and Ca2+ and K+ currents were blocked by external Co2+ (3 mM) and internal Cs+ (140 mM), respectively. I Na was elicited by depolarizing voltage steps from a holding potential of −100mV at a temperature of 33 °C. PamCar (5 μM) decreased the peak I Na (attained at −20mV or −30mV) from 6.1±2.1 nA to 3.9±1.4 nA (n=11), or by 36.1% within 2 min, and shifted the curve of steady-state I Na inactivation by 5.4 mV in the positive direction (from −76.3±4.6 mV, control to −70.9±4.0 mV, in PamCar, n=4). Partial restoration of the amplitude and the shift of the steady-state inactivation curve of I Na was attained after washout of PamCar. In contrast, lysoPtdCho at concentrations over 10 μM irreversibly depressed the I Na within 0.5–3 min and the reduction of IinNa was followed by cell contracture or cell death (n=9). The survival time, defined as a period from the start of lysoPtdCho application to the time of the last successful recording of the I Na (before evolution of sudden changes in the holding current), depended on the concentrations of lysoPtdCho. Both PamCar and lysoPtdCho retarded the time course of activation and inactivation of I Na. These findings are compatible with the idea that PamCar and lysoPtdCho decrease the maximum Na+ conductance and alter the surface negative charge of the membrane, perhaps via amphiphilic intervention in the phospholipid bilayers. However, PamCar had an additional effect that indicates more direct but reversible incorporation of this agent with the Na+ channels or integral membrane proteins.
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Sato, T., Kiyosue, T. & Arita, M. Inhibitory effects of palmitoylcarnitine and lysophosphatidylcholine on the sodium current of cardiac ventricular cells. Pflugers Arch. 420, 94–100 (1992). https://doi.org/10.1007/BF00378647
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DOI: https://doi.org/10.1007/BF00378647