Current, voltage and pharmacological substrates of a novel GABA receptor in the visual-vestibular system of Hermissenda

In the marine mollusc, Hermissenda crassicornis, Type B photoreceptors exhibit an IPSP to both presynaptic hair cell stimulation and microapplication of γ-aminobutyric acid (GABA) to the terminal branches. It was found that both the endogenous IPSP and the response to exogenously applied GABA were mediated to a large part by an outward current which reversed at approximately -80 mV. Additionally, these hyperpolarizing responses were found to mask a smaller depolarization that was mediated by the reduction of a basal outward current. Both the IPSP and the hyperpolarizing response to GABA, as well as the sublimated depolarizing response to GABA, were attenuated by the K⁺ channel blocker tetraethylammonium chloride (TEA) and displayed a strong sensitivity to [K⁺]₀, while showing no sensitivity to [Cl^-]₀ or the Cl^- channel blocker picrotoxin. Moreover, iontophoretic injections of stable guanine analogues, GTP[γS] and GDP[βS], into B photoreceptors eliminated both the IPSP and the GABA-induced hyperpolarization, while cholinergically mediated, interphotoreceptor interactions were unaffected. These results suggest that the endogenous receptor is at least partially homologous to the mammalian GABA_B class receptor. Consistent with this classification, microapplication of selective GABA_B receptor agonist baclofen onto the terminal region of the B photoreceptor resulted in a hyperpolarizing response that was qualitatively similar to that of GABA, although the GABA_A agonist muscimol was also active, but less so than either GABA or baclofen. Attempts to block the endogenous IPSP or GABA-induced hyperpolarization by bath application of the GABA_A receptor subtype antagonist bicuculline was ineffective and the GABA_B receptor subtype antagonist saclofen was only weakly effective. These data demonstrate that the presynaptic hair cell's influence on postsynaptic B photoreceptors is in many respects similar to GABA_B mediated responses in the mammalian CNS. This receptor is in some respects unique, however, in terms of its cross-sensitivity to both GABA_A and GABA_B agonists, its weak sensitivity to saclofen, and its apparent anomalous modulation of multiple K⁺ conductances.