The antidepressant imipramine inhibits the M-type K+ current in rat sympathetic neurons
- 1 July 2001
- journal article
- Published by Wolters Kluwer Health in NeuroReport
- Vol. 12 (10), 2195-2198
- https://doi.org/10.1097/00001756-200107200-00030
Abstract
This study aimed to assess the effects of the antidepressant drug imipramine (IMI) on the neuronal M-type K+ current (IK(M)). We show that IMI reversibly reduces IK(M) with an IC50 of 7 microM. The V0.5 and slope factor of the steady state activation curve remained unchanged after IMI, indicating a mode of action that is voltage insensitive for blocking the M-channel. Patch pipette application of IMI elicits same inhibitory response suggesting a binding site on the M-channel accessible from both sides of the cell membrane. Accordingly, the inhibitory effect of IMI is larger by rising external pH near to the pKa of the drug. Therefore, we propose that a neutral form of IMI binds more efficiently to M-channels to exert its inhibitory action by a voltage-independent mechanism.Keywords
This publication has 15 references indexed in Scilit:
- Inhibition of the current of heterologously expressed HERG potassium channels by imipramine and amitriptylineBritish Journal of Pharmacology, 1999
- Acute application of the tricyclic antidepressant desipramine presynaptically stimulates the exocytosis of glutamate in the hippocampusNeuroscience, 1999
- Imipramine Inhibition of Transient K+ Current: An External Open Channel Blocker Preventing Fast InactivationBiophysical Journal, 1998
- Bradykinin excites rat sympathetic neurons by inhibition of M current through a mechanism involving B2 receptors and Gαq/11Neuron, 1995
- Imipramine stimulates phospholipase C activity in rat brainNeurochemistry International, 1994
- Angiotensin II inhibits calcium and M current channels in rat sympathetic neurons via G proteinsNeuron, 1994
- Block of potassium currents in rat isolated sympathetic neurones by tricyclic antidepressants and structurally related compoundsBritish Journal of Pharmacology, 1993
- Protein kinase C is not necessary for peptide-induced suppression of M current or for desensitization of the peptide receptors.Proceedings of the National Academy of Sciences, 1989
- M-currents: an updateTrends in Neurosciences, 1988
- Control of the repetitive discharge of rat CA 1 pyramidal neurones in vitro.The Journal of Physiology, 1984