title: Inhibition of the calcineurin-like protein phosphatase activity in Limulus ventral eye photoreceptor cells alters the characteristics of the spontaneous quantal bumps and the light-mediated inward currents, and enhances arrestin phosphorylation.
abstract: Changes in intracellular calcium are involved in phototransduction processes in both vertebrate and invertebrate photoreceptors. During this phototransduction process in the Limulus ventral eye, there is a biochemical change in the protein phosphatase, calcineurin, such that it becomes capable of activation by calcium and calmodulin. Here we show that the calcium/calmodulin-dependent calcineurin-like activity in light-adapted ventral eye was completely inhibited by the CaN autoinhibitory peptide, CaN A457-482 and the Merck analog of the membrane-permeable, immunosuppressant drug, FK 506, L-683, 590, but not an inactive analogue, L-685, 818. Whole-cell, voltage-clamp recordings of spontaneous quantal bump activity present in dark-adapted photoreceptors injected with either CaN A457-482 (500 microM) or superfused with L-683, 590 (20 microM) or L-685, 818 revealed that both CaN A457-482 and L-683, 590, but not L-685, 818, caused rapid decreases in quantal bump amplitude, rise time and fall time, resulting in smaller, sharper bumps. This was correlated with enhanced phosphorylation of arrestin in light-adapted ventral eye photoreceptors exposed to L-683, 590 or less reliably okadaic acid. Both CaN A457-482 and L-683, 590 markedly affected the light-stimulated inward currents recorded from light-adapted ventral photoreceptors, causing a "terracing" of the inward current, and an intensity-dependent delay in the time required to reach peak amplitude. Consequently, inhibition of calcineurin markedly affects two major rhodopsin-dependent electrophysiological processes, and implicates CaN as an integral component in the phototransduction cascade.
authors.affiliation: Department of Biological Sciences, University of Maine, Orono, USA.
authors.forename: L
authors.initials: L
authors.lastname: Kass
authors.forename: D Z
authors.initials: DZ
authors.lastname: Ellis
authors.forename: J
authors.initials: J
authors.lastname: Pelletier
authors.forename: N E
authors.initials: NE
authors.lastname: Tableman
authors.forename: S C
authors.initials: SC
authors.lastname: Edwards
mesh_terms: D000818:Animals; D019393:Arrestin / Q000378:metabolism*; D019703:Calcineurin / Q000737:chemistry / Q000494:pharmacology; D065095:Calcineurin Inhibitors; D004594:Electrophysiology; D006737:Horseshoe Crabs / Q000378:metabolism*; D008027:Light; D010446:Peptide Fragments / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D017956:Photoreceptor Cells, Invertebrate / Q000166:cytology / Q000378:metabolism / Q000502:physiology* / Q000528:radiation effects; D016559:Tacrolimus / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D019393:Arrestin; D065095:Calcineurin Inhibitors; D010446:Peptide Fragments; C079136:L 683590; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; D016559:Tacrolimus