title: Protein kinase A mediates voltage-dependent facilitation of Ca2+ current in presynaptic hair cells in Hermissenda crassicornis.
abstract: The simplest cellular model for classical conditioning in the nudibranch mollusk, Hermissenda crassicornis, involves the presynaptic hair cells and postsynaptic photoreceptors. Whereas the cellular mechanisms for postsynaptic photoreceptors have been studied extensively, the presynaptic mechanisms remain uncertain. Here, we determined the phenotype of the voltage-dependent Ca(2+) current in the presynaptic hair cells that may be directly involved in changes in synaptic efficacy during classical conditioning. The Ca(2+) current can be classified as a P-type current because its activation voltage under seawater recording conditions is approximately -30 mV, it showed slow inactivation, and it is reversibly blocked by omega-agatoxin-IVA. The steady-state activation and inactivation curves revealed a window current, and the single-channel conductance is approximately 20 pS. The P-type current was enhanced by cAMP analogs (approximately 1.3-fold), and by forskolin, an activator of adenylyl cyclase (approximately 1.25-fold). In addition, the P-type current showed voltage-dependent facilitation, which is mediated by protein kinase A (PKA). Specifically, the PKA inhibitor peptide [PKI(6-22)amide] blocked the enhancement of the Ca(2+) current produced by conditioning depolarization prepulses. Because neurotransmitter release is mediated by Ca(2+) influx via voltage-gated Ca(2+) channels, and because of the nonlinear relationship between the Ca(2+) influx and neurotransmitter release, we propose that voltage-dependent facilitation of the P-type current in hair cells would produce a robust change in synaptic efficacy.
authors.affiliation: Center for Neuroscience, Department of Otolaryngology, University of California, Davis, California 95616, USA.
authors.forename: Catherine T
authors.initials: CT
authors.lastname: Tamse
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Xu
authors.forename: Haitao
authors.initials: H
authors.lastname: Song
authors.forename: Liping
authors.initials: L
authors.lastname: Nie
authors.forename: Ebenezer N
authors.initials: EN
authors.lastname: Yamoah
mesh_terms: D000818:Animals; D001464:Barium / Q000493:pharmacokinetics; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020865:Calcium Channels, P-Type / Q000378:metabolism; D003214:Conditioning, Classical / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D006198:Hair Cells, Auditory / Q000201:enzymology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008974:Mollusca; D009553:Nimodipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000201:enzymology
chemical_list: D002121:Calcium Channel Blockers; D020865:Calcium Channels, P-Type; D001464:Barium; D009553:Nimodipine; D017868:Cyclic AMP-Dependent Protein Kinases; D002118:Calcium