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Palmitoyl‐ dl ‐carnitine has calcium‐dependent effects on cultured neurones from rat dorsal root ganglia
Author(s) -
Stapleton Simon R.,
Currie Kevin P.M.,
Scott Roderick H.,
Bell B. Anthony
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb13427.x
Subject(s) - egta , biophysics , extracellular , calcium , dorsal root ganglion , chemistry , intracellular , voltage dependent calcium channel , barium , medicine , biochemistry , biology , anatomy , dorsum , inorganic chemistry , organic chemistry
1 The effects of palmitoyl‐ dl ‐carnitine (0.01 to 1 m m ) on whole cell voltage‐activated calcium channel currents carried by calcium or barium and Ca 2+ ‐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 Ca 2+ currents activated over a wide voltage range from a holding potential of −90 mV. Inhibition of high voltage activated Ca 2+ channel currents was dependent on intracellular Ca 2+ buffering and was reduced by increasing the EGTA concentration from 2 to 10 m m in the patch solution. Barium currents were significantly less sensitive to palmitoyl‐ dl ‐carnitine than Ca 2+ currents. 3 The amplitude of Ca 2+ ‐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 Ca 2+ from the cytoplasm following Ca 2+ entry through voltage‐activated channels. 4 Palmitoyl‐ dl ‐carnitine evoked Ca 2+ ‐dependent inward currents which could be promoted by activation of the residual voltage‐activated Ca 2+ currents and attenuated by intracellular application of EGTA. 5 We conclude that palmitoyl‐ dl ‐carnitine reduced the efficiency of intracellular Ca 2+ handling in cultured dorsal root ganglion neurones and resulted in enhancement of Ca 2+ ‐dependent events including inactivation of voltage‐activated Ca 2+ currents. The activation of inward currents by palmitoyl‐ dl ‐carnitine may involve Ca 2+ ‐induced Ca 2+ release from intracellular stores, or direct interaction of palmitoyl‐ dl ‐carnitine with Ca 2+ stores.