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

1 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. 2 Palmitoyl‐dl‐carnitine applied to the extracellular envi...

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Veröffentlicht in:British journal of pharmacology 1992-12, Vol.107 (4), p.1192-1197
Hauptverfasser: Stapleton, Simon R., Currie, Kevin P.M., Scott, Roderick H., Bell, B. Anthony
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Sprache:eng
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Zusammenfassung:1 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. 2 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. 3 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. 4 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. 5 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.
ISSN:0007-1188
1476-5381
DOI:10.1111/j.1476-5381.1992.tb13427.x