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

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 (IC50) of THB was 1.3x10(-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 THE non-competitively inhibits the ACh-induced K+ current in a concentration-dependent manner, and that this inhibitory effect provides further evidence that THE plays its pharmacological roles in the central nervous system by effects other than through blockade of dopamine receptors. (C) 1997 Elsevier Science Ireland Ltd.