DIVERSE CURRENT AND VOLTAGE RESPONSES TO BACLOFEN IN AN IDENTIFIED MOLLUSCAN PHOTORECEPTOR

1. gamma-Aminobuturic acid-B (GABA(B)) receptors play a role in the me diation of slow inhibitory postsynaptic potentials in mammalian as wel l as some nonmammalian species. In identified photoreceptors from the marine mollusc Hermissenda, recent evidence has suggested that GABA, a s well as the GABA(B) receptor agonist baclofen, might simultaneously modulate multiple conductances on the postsynaptic membrane. Here, usi ng intracellular current-clamp and single-electrode voltage-clamp tech niques, we have characterized responses to baclofen in the B photorece ptors of the Hermissenda eye. 2. Microapplication of baclofen (12.5-62 .5 mu M) to the terminal branches of the B photoreceptors induced a sl ow, concentration-dependent hyperpolarization (approximate to 3-8 mV) that was accompanied by a cessation of spontaneous action potentials a nd a positive shift in firing threshold. Both the hyperpolarization an d the shift in spike threshold in response to baclofen were attenuated largely by the K+ channel blocker tetraethylammonium chloride (TEA; 5 0 mM). 3. Bath application of baclofen (100 mu M) decreased the amplit ude, duration, and the afterhyperpolarization (AHP) of evoked action p otentials. Although baclofen's effect on spike duration and amplitude persisted in the absence of extracellular Ca2+, the reduction of the A HP by baclofen was eliminated, suggesting that multiple conductances m ediated the baclofen-induced modification of the action potential. 4. Using a single-electrode voltage-clamp technique, microapplication of baclofen to the terminal branches of the B photoreceptor produced a sl ow, net outward current (<0.5 nA) that reversed near the equilibrium p otential for K+ and shifted to more positive potentials when extracell ular K+ was increased, in approximate agreement with the Nernst equati on for K+. 5. Baclofen induced an increase in amplitude of the nonvolt age dependent leak conductance (I-L), and the increase was blocked by TEA. The baclofen-induced increase of I-L was accompanied by an increa se in amplitude and a negative shift in the voltage dependence of a sl ow, steeply voltage-dependent K+ current (I-K), which displays selecti ve sensitivity to TEA but does not normally contribute to leak conduct ance. The amplitude and steady-state inactivation of a fast, transient K+ current, as well as the amplitude of an inwardly rectifying K+ cur rent were unaffected by baclofen. 6. Both the rate of activation as we ll as the amplitude of a voltage-dependent Ca2+ current (I-ca) were re duced by baclofen. The reduction of I-ca resulted in a concomitant sup pression of a Ca2+-dependent K+ current (I-k-ca) that was sufficient t o account for the reduction of the AHP after evoked action potentials. 7. In total, these results suggest that the baclofen-induced hyperpol arization and spike narrowing are attributable to a postsynaptic incre ase in K+ conductance, possibly through the I-K class channel, whereas a reduction of the AHP results from a decrease in I-K-ca that is attr ibutable to a reduction in voltage-dependent Ca2+ influx. These respon ses, as well as the direct reduction of I-ca by baclofen, are likely t o result in a functional decrease in intracellular Ca2+ concentration during an action potential, suppressing secretion onto postsynaptic ta rgets. Thus GABA(B) receptors on these neurons may contribute to both pre- and postsynaptic forms of inhibition.