The Journal of Neurophysiology Vol. 86 No. 3 September 2001, pp. 1297-1311
Copyright ©2001 by the American Physiological Society

PP1 Inhibitors Depolarize Hermissenda Photoreceptors and Reduce K⁺ Currents

Neural Science, Indiana University, Bloomington, Indiana 47405-7007

Huang, Haojiang and Joseph Farley. PP1 Inhibitors Depolarize Hermissenda Photoreceptors and Reduce K⁺ Currents. J. Neurophysiol. 86: 1297-1311, 2001. 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.