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 (IACh) is sensitive to the muscarinic receptor antagonist, atropine and the K+ channel blocker, TEA. The reversal potential of IACh (-84.1 +/- 0.8 mV) is close to the K+ equilibrium potential, indicating that the IACh is mediated by a muscarinic receptor, and is carried mainly by K+. Tetrahydroberberine (THB) markedly reduced the IACh while its chemical analogs, l-stepholidine (l-SPD) or l-tetrahydropalmatine (l-THP), had little effect on the IACh. The half-maximal inhibitory concentration (IC50) of THB was 1.3 x 10(-5) M for a 10(-5) M ACh-induced IACh. 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.
Wu
J
J
Department of Neurology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA. wujie@unm.edu
Jin
G Z
GZ
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001599:Berberine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D006624:Hippocampus / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism*; D017966:Pyramidal Cells / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D051381:Rats
D002121:Calcium Channel Blockers; D001599:Berberine; D000109:Acetylcholine; D011188:Potassium; C004645:canadine