Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 452, Issue 1, Pages 35-48Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0014-2999(02)02239-2
Keywords
Na+ channel; K channel; antidepressant; imipramine; patch clamping; Na-22(+) flux
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The effects of a range of antidepressants were investigated on neuronal voltage-gated Na+ and K+ channels. With the exception of phenelzine, all antidepressants inhibited batrachotoxin-stimulated Na-22(+) uptake, most likely via negative allosteric inhibition of batrachotoxin binding to neurotoxin receptor site-2 on the Na+ channel. Imipramine also produced a differential action on macroscopic Na+ and K+ channel currents in acutely dissociated rat dorsal root ganglion neurons. Imipramine produced a use-dependent block of Na+ channels. In addition, there was a hyperpolarizing shift in the voltage-dependence of steady-state Na+ channel inactivation and slowed repriming kinetics consistent with imipramine having a higher affinity for the inactivated state of the Na+ channel. At higher concentrations, imipramine also blocked delayed-rectifier and transient outward K+ currents in the absence of alterations to the voltage-dependence of activation or the kinetics of inactivation. These actions on voltage-gated ion channels may underlie the therapeutic and toxic effects of these drugs. (C) 2002 Elsevier Science B.V. All rights reserved.
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