PP1 inhibitors depolarize Hermissenda photoreceptors and reduce K+ currents.
Previous research indicates that activation of protein kinase C (PKC) plays a critical role in the induction and maintenance of memory-related changes in neural excitability of Type B photoreceptors in the eyes of nudibranch mollusk Hermissenda crassicornis (H.c.). The enhanced excitability of B cells is due in part to PKC-mediated reduction in somatic K+ currents. Here we examined the effects of protein phosphatase inhibitors on Type B photoreceptor excitability and K+ currents to determine the role(s) of protein phosphatases on memory formation in Hermissenda. Using electrophysiological and pharmacological methods, we found that the PP1 inhibitors calyculin A and inhibitor-2 depolarized Type B photoreceptors by 20-30 mV. A broad-spectrum kinase inhibitor, H7, blocked this effect. The depolarization induced by PP1 inhibition occluded that produced by an in vitro associative conditioning procedure. Calyculin and inhibitor-2 reduced the same B cell K+ currents (I(A) and I(delayed)) that are reduced by in vitro and behavioral conditioning. H7 blocked the reductions. Cantharidic acid (PP2A inhibitor) and cyclosporin (PP2B inhibitor) had negligible effects on B cell resting membrane potential, K+ currents, and in vitro conditioning-produced cumulative depolarization of B cells. These results suggest that the functional activity of K+ channels in B cells is sustained by basal activity of PP1. Inhibiting PP1 appears to allow one or more constitutively active kinase(s) to reduce K+ channel activity and thus mimic the effects of conditioning. Our results suggest that PP1 may oppose and/or constrain the extent of learning-produced changes in B cell excitability.
Huang
H
H
Neural Science, Indiana University, 1101 E. 10th St., Bloomington, IN 47405-7007, USA.
Farley
J
J
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000818:Animals; D002193:Cantharidin / Q000494:pharmacology; D002868:Chromosomal Proteins, Non-Histone; D003213:Conditioning, Psychological / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors / Q000494:pharmacology; D056488:Histone Chaperones; D008387:Marine Toxins; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008974:Mollusca; D010080:Oxazoles / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D017956:Photoreceptor Cells, Invertebrate / Q000502:physiology*; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D011506:Proteins / Q000494:pharmacology; D014157:Transcription Factors
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D056488:Histone Chaperones; D008387:Marine Toxins; D010080:Oxazoles; D015221:Potassium Channels; D011506:Proteins; C513473:SET protein, human; D014157:Transcription Factors; C059041:calyculin A; D016572:Cyclosporine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D010749:Phosphoprotein Phosphatases; D002193:Cantharidin; D011188:Potassium