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)-i nduced current were studied in freshly dissociated pyramidal neurons f rom 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 antago nist, 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, in dicating that the I-ACh is mediated by a muscarinic receptor, and is c arried mainly by K+. Tetrahydroberberine (THB) markedly reduced the I- ACh while its chemical analogs, l-stepholidine (l-SPD) or l-tetrahydro palmatine (l-THP), had little effect on the I-ACh. The half-maximal in hibitory concentration (IC50) of THB was 1.3x10(-5) M for a 10(-5) M A Ch-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 in hibits the ACh-induced K+ current in a concentration-dependent manner, and that this inhibitory effect provides further evidence that THE pl ays its pharmacological roles in the central nervous system by effects other than through blockade of dopamine receptors. (C) 1997 Elsevier Science Ireland Ltd.