[Abstract Title]. - Society for Neuroscience

Program#/Poster#: 234.14/C38
Topic: B.04.c. Potassium channels: Physiology
Support: NS045217
Title: Characterization of a DPPX (DPP6) splice variant producing A-type currents with faster
inactivation
Authors: J. K. MAFFIE 1 , *B. RUDY 2 ;
1 Smilow NeuroscienceProgram, Dept. Physiol. and Neurosci., NYU Sch. of Med., New York,
NY; 2 Physiol & Neurosci, NYU Sch. Med., New York, NY
Abstract: Transient A-type K(+) currents (I(SA)s) have fundamental roles in neuronal function.
These subthreshold-activating, somato-dendritic currents produce delayed excitation, influence
spike repolarization, modulate the frequency of repetitive firing, and are proposed to have
important roles in signal processing in dendrites. We previously reported that DPPX proteins are
key components of Kv4 channels, the channels that produce these A-type currents. (Nadal, M.S.,
Ozaita, A., Amarillo, Y., Vega-Saenz, E., Ma, Y., Mo, W., Goldberg, E.M., Misumi, Y., Ikehara,
Y., Neubert, T.A., Rudy, B., 2003. The CD26-related dipeptidyl aminopeptidase-like protein
DPPX is a critical component of neuronal A-type K+ channels. Neuron 37, 449-461). The DPPX
gene encodes alternatively spliced transcripts that generate single-spanning transmembrane
proteins with a short, splice specific intracellular domain and a large extracellular domain. The
modulatory effects on Kv4.2-mediated currents and the rat brain distribution of three splice
variants of the DPPX subfamily of protein have previously been described. (Nadal MS, Amarillo
Y, Vega-Saenz de Miera E, Rudy B., 2006. Differential characterization of three alternative
spliced isoforms of DPPX. Brain Res. 13;1094). The kinetics and voltage dependence of the
currents produced by channels containing these isoforms were shown to be very similar in the
presence or absence of KChIPs, the other putitive accessory protein of Kv4 channels. We cloned
cDNA of an additional DPPX isoform, DPPX-E, and studied the ability of DPPX-E protein to
modulate the properties of Kv4.2 channels in heterologous expression systems. We show that the
kinetics of inactivation is dramatically faster than those produced by Kv4 channels expressed
with other splice forms of DPPX. This parallels a similar acceleration seen in the DPP10-A
splice variant, a protein with a similar role in Kv4 complexes. The DPP10-A splice variant has
significant sequence similarity to DPPX-E supporting the finding that they have similar effects
on the Kv4 current. The location of this isoform in mouse brain was explored using in situ
hybridization. The diversity of DPPX splice variants opens up intriguing possibilities for the
modulation of Kv4 channels and thereby for diversity in the electrophysiologic processes
modulated by this current.
Disclosures: J.K. Maffie, None; B. Rudy , None.
Poster