Tandospirone-induced K⁺ current in acutely dissociated rat dorsal raphe neurones

Abstract

1. The effects of tandospirone (TDS) on dissociated rat dorsal raphe neurones were investigated using the patch-clamp method.

2. Under current-clamp conditions, TDS hyperpolarized the cell membrane, resulting in the reduction of firing rates.

3. Under voltage-clamp conditions, TDS induced an inward rectifying K⁺ current in a concentration-dependent manner.

4. The TDS-induced K⁺ currents (I_TDS) were mimicked by 8-OH-DPAT, a 5-HT_1A agonist. The I_TDS was blocked by spiperone, a 5-HT_1A receptor antagonist, in a concentration-dependent manner.

5. N-Ethylmaleimide, an agent which uncouples between the receptor and the G-protein, irreversibly blocked the I_TDS.

6. In neurones perfused intracellularly with a pipette-solution containing GTP using the conventional whole-cell patch recording, the I_TDS showed a gradual rundown. When the neurones were perfused with GTPγS, TDS activated the inwardly rectifying K⁺ current in an irreversible manner.

7. In the inside-out patch recording mode, TDS-activated single K⁺ channel currents (i_TDS) which also showed an inward rectification. When the GDP in cytosolic side was completely replaced with GTP, the open probability of i_TDS significantly increased.

8. These results indicate that the activation of 5-HT_1A receptors by TDS directly opens the inward rectifying K⁺ channels via a G-protein mediated process.

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