Inhibition of the 5-HT(1A) receptor-mediated inwardly rectifying K(+) current by dextromethorphan in rat dorsal raphe neurones.
H Ishibashi, K Kuwano, K Takahama
Neuropharmacology September 2000 DOI: 10.1016/s0028-3908(00)00092-7 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro electrophysiological study Peer reviewed |
|---|---|
| Population | Acutely dissociated dorsal raphe neurones and freshly isolated locus coeruleus neurones of rats |
| Intervention | Dextromethorphan |
| Topics | Serotonin |
| Key points | Dextromethorphan inhibited 5-HT-induced inwardly rectifying potassium currents in rat dorsal raphe neurons with a half-maximum inhibitory concentration of 1.43 x 10^-5 M, acting non-competitively and also suppressing GTPgammaS-activated currents and alpha(2)-adrenoceptor-regulated currents. The authors suggest DM acts on G-protein coupled inwardly rectifying potassium channels rather than on neurotransmitter receptors. |
Abstract
The effect of dextromethorphan (DM) on the inwardly rectifying K(+) currents mediated by 5-HT(1A) receptors in acutely dissociated dorsal raphe (DR) neurones of rats was studied using nystatin-perforated patch and conventional whole-cell patch recording configurations under voltage-clamp conditions. DM rapidly and reversibly inhibited the K(+) currents induced by 10(-7) M 5-HT in a concentration-dependent manner with a half-maximum inhibitory concentration of 1.43 x 10(-5) M. The inhibitory effect of DM was neither voltage- nor use-dependent. DM caused a suppression of the maximum response of the 5-HT concentration-response curve, thus suggesting a non-competitive type of inhibition. In neurones perfused intracellularly with a pipette-solution containing the nonhydrolyzable GTP analog GTPgammaS, 5-HT activated K(+) currents in an irreversible manner. DM suppressed the current irreversibly activated by intracellular GTPgammaS even in the absence of the agonist. DM also inhibited the inwardly rectifying K(+) currents regulated by alpha(2)-adrenoceptors in freshly isolated rat locus coeruleus neurones. These results suggest that DM may inhibit the G-protein coupled inwardly rectifying K(+) channels, but not the neurotransmitter receptors, in the central nervous system.
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