Intracellular QX-314 inhibits calcium currents in hippocampal CA1 pyramidal neurons.
1. The effects of intracellular QX-314 on Ca2+ currents were examined in CA1 pyramidal cells acutely isolated from rat hippocampus. In neurons dialyzed with 10 mM QX-314 (bromide salt), the amplitude of the high-threshold Ca2+ current was on average 20% of that in control cells and the current-voltage relationships (I-Vs) were shifted in the positive voltage direction. 2. The positive shift in the I-Vs was due to the presence of intracellular Br-, because it was reproduced by 10 mM NaBr and was not present when the chloride salt of QX-314 was used. 3. Low-threshold (T-type) Ca2+ currents, at test voltages of -50 and -40 mV, were on average < 45% of control amplitude in cells containing 10 mM QX-314 (chloride salt) and < 10% of control amplitude in cells with 10 mM QX-314 (bromide salt). 4. In neurons dialyzed with 1 mM QX-314, high-threshold Ca2+ currents were still significantly different from control and Na+ currents were not completely blocked. 5. The proportions of high-threshold Ca2+ current blocked by omega-conotoxin GVIA, omega-agatoxin IVA, and nimodipine were similar in cells dialyzed with 10 mM QX-314 and control cells, indicating that the drug does not selectively inhibit any of the Ca2+ channel subtypes distinguished by these antagonists.
Talbot
M J
MJ
Department of Physiology, University of Otago, Dunedin, New Zealand.
Sayer
R J
RJ
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008012:Lidocaine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008564:Membrane Potentials / Q000502:physiology; D008959:Models, Neurological; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism
D000779:Anesthetics, Local; D002121:Calcium Channel Blockers; D015222:Sodium Channels; C012647:QX-314; D008012:Lidocaine