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 elicit desensitizing Cl-dependent responses. This fact and the finding that the 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 intracellular sulfate. Exploiting these distinctive characteristics and the independent expression of the receptors in some cells, we have been able to reevaluate the so-called cross-desensitization by analyzing the ability of GABA, glutamate, and other agonists to interact with each of the receptor molecules. The cross-desensitization was found to be exclusively attributable to the ability of GABA to interact with the glutamate receptor (Oyama et al., 1990). The GABA receptor is unaffected by glutamate. Nevertheless, in cells expressing both receptors, glutamate can reduce the GABA response by auto-desensitizing the part of the response that is mediated by the glutamate receptor. No interactions were observed between ACh-induced responses and either of 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 pharmacological evaluation of the molluscan glutamate receptor points in the same direction.