Protein Kinase A Mediates Voltage-Dependent Facilitation of Ca2+ Current in Presynaptic Hair Cells in Hermissenda crassicornis

1 Center for Neuroscience, Department of Otolaryngology and 2 Department of Medicine, Division of Cardiology, University of California, Davis, California 95616; and 3 Marine Biological Laboratory, Woods Hole, Massachusetts 02543 Tamse, Catherine T., Yanfang Xu, Haitao Song, Liping Nie, and Ebenezer N. Yamoah. Protein Kinase A Mediates Voltage-Dependent Facilitation of Ca 2+ Current in Presynaptic Hair Cells in Hermissenda crassicornis . J. Neurophysiol. 89: 1718-1726, 2003. 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 -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.