AMRP peptides modulate a novel K(+) current in pleural sensory neurons of Aplysia

Modulation of Aplysia mechanosensory neurons is thought to underlie plasticity of defensive behaviors that are mediated by these neurons. In the past, identification of modulators that act on the sensory neurons and characterization of their actions has been instrumental in providing insight into the functional role of the sensory neurons in the defensive behaviors. Motivated by this precedent and a recent report of the presence of Aplysia Mytilus inhibitory peptide-related (AMRP) neuropeptides in the neuropile and neurons of the pleural ganglia, we sought to determine whether and how pleural sensory neurons respond to the AMRPs. In cultured pleural sensory neurons under voltage clamp, AMRPs elicited a relatively rapidly developing, then partially desensitizing, outward current. The current exhibited outward rectification; in normal 10 mM K(+), it was outward at membrane potentials more positive than -80 mV but disappeared without reversing at more negative potentials. When external K(+) was elevated to 100 mM, the AMRP-elicited current reversed around -25 mV; the shift in reversal potential was as expected for a current carried primarily by K(+). In the high-K(+) solution, the reversed current began to decrease at potentials more negative than -60 mV, creating a region of negative slope resistance in the I-V relationship. The AMRP-elicited K(+) current was blocked by extremely low concentrations of 4-aminopyridine (4-AP; IC(50) = 1.7 x 10(-7) M) but was not very sensitive to TEA. In cell-attached patches, AMRPs applied outside the patch-thus presumably through a diffusible messenger-increased the activity of a K(+) channel that very likely underlies the macroscopic current. The single-channel current exhibited outward rectification, and the open probability of the channel decreased with hyperpolarization; together, these two factors accounted for the outward rectification of the macroscopic current. Submicromolar 4-AP included in the patch pipette blocked the channel by reducing its open probability without altering the single-channel current. Based on the characteristics of the AMRP-modulated K(+) current, we conclude that it is a novel current that has not been previously described in Aplysia mechanosensory neurons. In addition to this current, two other AMRP-elicited currents, a slow, 4-AP-resistant outward current and a Na(+)-dependent inward current, were occasionally observed in the cultured sensory neurons. Responses consistent with all three currents were observed in sensory neurons in situ in intact pleural ganglia.