Tetrahydroberberine inhibits acetylcholine-induced K + current in acutely dissociated rat hippocampal CA1 pyramidal neurons

Abstract

The effects of a novel chemical type of dopamine receptor antagonist, the tetrahydroprotoberberine analogs (THPBs), on acetylcholine (ACh)-induced current were studied in freshly dissociated pyramidal neurons from rat hippocampal CA1 area using the nystatin perforated patch-clamp recording technique. Under voltage clamp conditions, the ACh-induced outward current ( I ACh) is sensitive to the muscarinic receptor antagonist, atropine and the K + channel blocker, TEA. The reversal potential of I ACh (−84.1±0.8 mV) is close to the K + equilibrium potential, indicating that the I ACh is mediated by a muscarinic receptor, and is carried mainly by K +. Tetrahydroberberine (THB) markedly reduced the I ACh while its chemical analogs, l-stepholidine ( l-SPD) or l-tetrahydropalmatine ( l-THP), had little effect on the I ACh. The half-maximal inhibitory concentration (IC 50) of THB was 1.3×10 −5 M for a 10 −5 M ACh-induced I ACh. THB suppressed the maximum of the ACh concentration-response curve without shifting the Hill coefficient, indicating a non-competitive inhibition. It is concluded that THB non-competitively inhibits the ACh-induced K + current in a concentration-dependent manner, and that this inhibitory effect provides further evidence that THB plays its pharmacological roles in the central nervous system by effects other than through blockade of dopamine receptors.