CURRENT, VOLTAGE AND PHARMACOLOGICAL SUBSTRATES OF A NOVEL GABA RECEPTOR IN THE VISUAL-VESTIBULAR SYSTEM OF HERMISSENDA

In the marine mollusc, Hermissenda crassicomis, Type B photoreceptors exhibit an IPSP to both presynaptic hair cell stimulation and microapp lication of gamma-aminobutyric acid (GABA) to the terminal branches. I t was found that both the endogenous IPSP and the response to exogenou sly applied GABA were mediated to a large part by an outward current w hich reversed at approximately - 80 mV. Additionally, these hyperpolar izing responses were found to mask a smaller depolarization that was m ediated by the reduction of a basal outward current. Both the IPSP and the hyperpolarizing response to GABA, as well as the sublimated depol arizing response to GABA, were attenuated by the K+ channel blocker te traethylammonium chloride (TEA) and displayed a strong sensitivity to [K+](0), while showing no sensitivity to [Cl-](0) or the Cl- channel b locker picrotoxin. Moreover, iontophoretic injections of stable guanin e analogues, GTP[gamma S] and GDP[beta S], into B photoreceptors elimi nated both the IPSP and the GABA-induced hyperpolarization, while chol inergically mediated, interphotoreceptor interactions were unaffected. These results suggest that the endogenous receptor is at least partia lly homologous to the mammalian GABA(B) class receptor. Consistent wit h this classification, microapplication of selective GABA(B) receptor agonist baclofen onto the terminal region of the B photoreceptor resul ted in a hyperpolarizing response that was qualitatively similar to th at of GABA, although the GABA(A) agonist muscimol was also active, but less so than either GABA or baclofen. Attempts to block the endogenou s IPSP or GABA-induced hyperpolarization by bath application of the GA BA(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 resp ects unique, however, in terms of its cross-sensitivity to both GABA(A ) and GABA(B) agonists, its weak sensitivity to saclofen, and its appa rent anomalous modulation of multiple K+ conductances.