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 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 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 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 Ca2+ from the cytoplasm following Ca2+ 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 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 Ca(2+)-dependent events including inactivation of voltage-activated Ca2+ currents. The activation of inward currents by palmitolyl-DL-carnitine may involve Ca(2+)-induced Ca2+ release from intracellular stores, or direct interaction of palmitoyl-DL-carnitine with Ca2+ stores.
Stapleton
S R
SR
Department of Physiology, St George's Hospital Medical School, London.
Currie
K P
KP
Scott
R H
RH
Bell
B A
BA
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects*; D002478:Cells, Cultured; D004594:Electrophysiology; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010172:Palmitoylcarnitine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D015220:Calcium Channels; D010172:Palmitoylcarnitine; D002110:Caffeine; D002118:Calcium