Independence of and interactions between GABA-, glutamate-, and acetylcholine-activated Cl conductances in Aplysia neurons

In certain Aplysia neurons, glutamate, GABA, and acetylcholine (ACh) all el icit desensitizing Cl-dependent responses. This fact and the finding that t he glutamate and GABA responses "cross-desensitize" led to the suggestion ( Swann and Carpenter, 1975; King and Carpenter, 1987) that the responses to these transmitters were mediated by the same receptor-channel complex. This hypothesis is incompatible with the demonstration given here that the GABA- and glutamate-gated channels are clearly distinct; the GABA channel, but not the glutamate channel, shows outward rectification (Matsumoto, 1982 ; King and Carpenter, 1987, 1989) and is selectively blocked by intracellul ar sulfate. Exploiting these distinctive characteristics and the independen t expression of the receptors in some cells, we have been able to reevaluat e the so-called cross-desensitization by analyzing the ability of GABA, glu tamate, and other agonists to interact with each of the receptor molecules. The cross-desensitization was found to be exclusively attributable to the a bility of GABA to interact with the glutamate receptor (Oyama et al., 1990) . The GABA receptor is unaffected by glutamate. Nevertheless, in cells expr essing both receptors, glutamate can reduce the GABA response by auto-desen sitizing the part of the response that is mediated by the glutamate recepto r. No interactions were observed between ACh-induced responses and either o f the responses elicited by the amino acids. The invertebrate glutamate-gated Cl channels that have been cloned resemble the vertebrate glycine receptor (Vassilatis et al., 1997). Our pharmacolog ical evaluation of the molluscan glutamate receptor points in the same dire ction.