Antagonistic Modulation of a Hyperpolarization-Activated Cl– Current in Aplysia Sensory Neurons by SCPB and FMRFamide

Abstract

Whole cell voltage-clamp recordings from Aplysia mechanosensory neurons obtained from the pleural ganglion were used to investigate the actions on membrane currents of the neuropeptides SCPB and FMRFamide. At the start of whole cell recording, SCPB typically evoked an inward current at a holding potential of –40 mV, due to the cAMP-mediated closure of the S-type K+ channel, whereas FMRFamide evoked an outward current, due to the opening of the S-type K+ channels mediated by 12-lipoxygenase metabolites of arachidonic acid. However, after several minutes of whole cell recording with a high concentration of chloride in the whole cell patch pipette solution, the responses to SCPB and FMRF-amide at –40 mV were inverted; SCPB evoked an outward current, whereas FMRFamide and YGGFMRFamide evoked inward currents. Ion substitution experiments and reversal potential measurements revealed that these responses were due to the opposing regulation of a Cl– current, whose magnitude was greatly enhanced by dialysis with the high Cl–-containing pipette solution. SCPB inhibited this Cl– current through production of cAMP and activation of PKA. YGGFMRFamide activated this Cl– current by stimulating a cGMP-activated phosphodiesterase that hydrolyzed cAMP. Thus a cAMP-dependent Cl– current undergoes antagonistic modulation by two neuropeptides in Aplysia sensory neurons.