Abstract
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 22Na + 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.
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