Palmitoyl‐dl‐carnitine has calcium‐dependent effects on cultured neurones from rat dorsal root ganglia

The effects of palmitoyl‐dl‐carnitine (0.01 to 1 mm) on whole cell voltage‐activated calcium channel currents carried by calcium or barium and Ca²⁺‐activated chloride currents were studied in cultured neurones from rat dorsal root ganglia. Palmitoyl‐dl‐carnitine applied to the extracellular environment or intracellularly via the patch solution reduced Ca²⁺ currents activated over a wide voltage range from a holding potential of −90 mV. Inhibition of high voltage activated Ca²⁺ channel currents was dependent on intracellular Ca²⁺ buffering and was reduced by increasing the EGTA concentration from 2 to 10 mm in the patch solution. Barium currents were significantly less sensitive to palmitoyl‐dl‐carnitine than Ca²⁺ currents. The amplitude of Ca²⁺‐activated Cl⁻ tail currents was reduced by palmitoyl‐dl‐carnitine. However, the duration of these Cl⁻ currents was greatly prolonged by palmitoyl‐dl‐carnitine, suggesting slower removal of free Ca²⁺ from the cytoplasm following Ca²⁺ entry through voltage‐activated channels. Palmitoyl‐dl‐carnitine evoked Ca²⁺‐dependent inward currents which could be promoted by activation of the residual voltage‐activated Ca²⁺ currents and attenuated by intracellular application of EGTA. We conclude that palmitoyl‐dl‐carnitine reduced the efficiency of intracellular Ca²⁺ handling in cultured dorsal root ganglion neurones and resulted in enhancement of Ca²⁺‐dependent events including inactivation of voltage‐activated Ca²⁺ currents. The activation of inward currents by palmitoyl‐dl‐carnitine may involve Ca²⁺‐induced Ca²⁺ release from intracellular stores, or direct interaction of palmitoyl‐dl‐carnitine with Ca²⁺ stores. 1992 British Pharmacological Society