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Differential blockade of neuronal voltage-gated Na+ and K+ channels by antidepressant drugs
- Source :
-
European Journal of Pharmacology . Sep2002, Vol. 452 Issue 1, p35-48. 14p. - Publication Year :
- 2002
-
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. [Copyright &y& Elsevier]
- Subjects :
- *SODIUM channels
*POTASSIUM channels
*ANTIDEPRESSANTS
Subjects
Details
- Language :
- English
- ISSN :
- 00142999
- Volume :
- 452
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- European Journal of Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 7882474
- Full Text :
- https://doi.org/10.1016/S0014-2999(02)02239-2