Tetrahydroberberine suppresses dopamine-induced potassium current in acutely dissociated CA1 pyramidal neurons from rat hippocampus

Effects of tetrahydroberberine (THB) on dopamine (DA)-induced response have been investigated in single pyramidal neurons freshly dissociated from CA1 area of the hippocampus using the nystatin perforated patch-clamp, whole-cell recording technique under voltage-clamp configuration. At a holding potential (V(H)) of -20 mV, DA-induced responses included a transient outward current, a slow inward current and a combination of the two. The outward current had a reversal potential of -83.5 ± 8.0 mV which was close to K⁺ equilibrium potential and was sensitive to TEA, suggesting that this outward current was carried by K⁺. Application of THB reversibly suppressed three type responses induced by DA with different degrees of inhibitory ratio, THB inhibited the DA-induced outward current in a concentration-dependent manner with an IC₅₀ of 13 μM. The maximal value of the concentration-response curve for DA-induced outward current was suppressed by THB, suggesting a non-competitive inhibition. The results support the hypothesis that THB acts as a novel dopaminergic system antagonist. Furthermore, THB inhibits the DA-induced K⁺ current non-competitively in single dissociated cells, implying that THB may exhibit other pharmacological action on the central nervous system.