Penicilin-induced triphasic modulation of GABA_A receptor-operated chloride current in frog sensory neuron

Effects of penicillin-G(PPCN) on GABA-evoked Cl^- current (I_GABA) were investigated in freshly dissociated frog sensory neurons by the use of the concentration-clamp technique combined with the suction-pipette method. Under conditions where the internal and external solutions allowed only Cl^- permeability, PCN elicited triphasic modulation on I_GABA, consisting of two modes of blockade on I_GABA and a following rebound (rebound-like transient I_GABA). Simultaneously applied PCN and GABA depressed I_GABA immediately (phasic blockade), with the depressed I_GABA slightly recovering in amplitude to achieve a stable level of blockade (tonic blockade). When a solution containing a mixture or PCN and GABA was quickly replaced by one containing GABA alone, a rebound-like transient Cl^- current (I_GABA) was evoked. Each component of the PCN actions on I_GABA was PCN- and GABA-concentration-dependent. The reversal potential for each component of the PCN actions on _GABA was close to the chloride equilibrium potential (E_Cl calculated using the Nernst equation. The current-voltage (I-V) relations for both the phasic and tonic blockade revealed inward rectification, while I-V curves for the control I_GABA and the I_R were outwardly rectified. The degree of I_GABA-desensitization and the amplitude of the I_R correlated well. The data suggest that partial removal of the GABA_A receptor-desensitization may result in generation of the I_R.