Desensitization of Cl(-)-dependent GABA response observed in ganglion cells of Aplysia

There are many cells in the abdominal ganglion which show a fast, Cl(-)-dependent hyperpolarizing response to gamma-aminobutyric acid (GABA). This response is characterized by an initial rapid increase in membrane conductance followed by an exponential decay to the original value despite a sustained application of GABA. The decay of the response was found to be largely due to the desensitization of the GABA receptor (binding site-ionophore complex) since the equilibrium potential for chloride remained unchanged when the conductance response was depressed. The apparent or measurable rate constant of desensitization (KD) increased when the concentration of GABA increased, showing a saturation in KD-[GABA] relationship at higher concentration of GABA. The rate of desensitization did not change significantly when the resting membrane was hyperpolarized from -40 to -80 mV, though the conductance response was markedly depressed due to a characteristic voltage-dependence in the receptor activation (Matsumoto, 1982). These observations are discussed in terms of an hypothesis in which the desensitization of GABA receptor is the result of an additional binding of a GABA molecule to the activated receptor.