Effects of penicillin G (PCN) on glycine (Gly)-evoked Cl- current (IGly) were investigated in acutely dissociated rat ventro-medial hypothalamic (VMH) neurones by the whole cell mode of patch clamp technique. 2. When PCN was applied simultaneously with Gly, PCN depressed IGly like a Cl- channel blocker. 3. The PCN-induced blocking action was clearly observed at a low PCN concentration (30 u), while the maximal blockade was achieved by 600 u (units per 10 ml) PCN. 4. When tested solution containing both PCN and Gly was quickly substituted with one containing Gly only, a new rebound-like transient current (I(T)) which also passed through Cl- channel, was elicited. 5. The peak amplitude of I(T) induced by PCN at concentrations higher than 100 u was greater than that induced by glycine alone. We termed this phenomenon PCN-induced potentiation of IGly. In all cells tested, PCN potentiated IGly. 6. At a lower PCN concentration below 30 u, I(T) generation was not clear in the presence of 10(-5) M gamma-aminobutyric acid. With PCN a higher concentration than 300 u, I(T) amplitude was greater than that of the original peak IGly. This was observed in 18 neurones out of 21. The maximal amplitude of the I(T) was achieved with 600 u PCN.
