Met-enkephalin and morphiceptin modulate a GABA-induced inward current in the CNS of Lymnaea stagnalis L

The interaction between GABA and opioid peptides (met-enkephalin and morphiceptin) was studied on the identified, isolated and internally perfused neurons of Lymnaea stagnalis L. (Gastropoda, Basommatophora). GABA (10^-7-10^-5 M) activated a Cl-dependent inward current with about -20 mV equilibrium potential. Slow and fast GABA-induced inward currents were recorded with different kinetic parameters in distinct identified neurons. Both types of GABA-induced inward currents were reduced or blocked by met-enkephalin (10^-7-10^-5 M) and morphiceptin (10^-7-10^-5 M) in a dose-dependent manner. GABA-activated fast inward current was modulated in a biphasic way in some neurons. Opioid reduction of the GABA-activated slow inward current was reversible, whereas the fast current was not. The reversible inhibition of the GABA-induced slow inward current produced by met-enkephalin or morphiceptin was naloxone (10^-5-10^-4 M)-sensitive, whereas the irreversible block of the fast GABA response was not antagonised by naloxone. Some additive effects between GABA and the peptides were also noted. The modulatory effect of the opioid peptides on the GABA response altered the peak current, the time-to-peak and inactivation time-course of the GABA-induced current. Thus, the identified, isolated and internally perfused neurons of Lymnaea stagnalis L. provide a useful model for studying postsynaptic mechanisms of interaction between GABA and opioid peptides. This interaction is a phenomenon of evolutionary significance because it is also found in mammals.