RT info:eu-repo/semantics/article
T1 A Role for DPPX Modulating External TEA Sensitivity of Kv4 Channels
A1 López López, José Ramón
A1 Colinas, Olaia
A1 Pérez Carretero, Francisco D.
A1 Pérez García, María Teresa
K1 Neurofisiología
AB Shal-type (Kv4) channels are expressed in a large variety of tissues, where they contribute to transient voltage- dependent K+ currents. Kv4 are the molecular correlate of the A-type current of neurons (ISA), the fast component of ITO current in the heart, and also of the oxygen-sensitive K+ current (KO2) in rabbit carotid body (CB) chemore- ceptor cells. The enormous degree of variability in the physiological properties of Kv4-mediated currents can be attributable to the complexity of their regulation together with the large number of ancillary subunits and scaffold- ing proteins that associate with Kv4 proteins to modify their trafficking and their kinetic properties. Among those, KChIPs and DPPX proteins have been demonstrated to be integral components of ISA and ITO currents, as their co- expression with Kv4 subunits recapitulates the kinetics of native currents. Here, we explore the presence and func- tional contribution of DPPX to KO2 currents in rabbit CB chemoreceptor cells by using DPPX functional knockdown with siRNA. Additionally, we investigate if the presence of DPPX endows Kv4 channels with new pharmacological properties, as we have observed anomalous tetraethylammonium (TEA) sensitivity in the native KO2 currents. DPPX association with Kv4 channels induced an increased TEA sensitivity both in heterologous expression systems and in CB chemoreceptor cells. Moreover, TEA application to Kv4-DPPX heteromultimers leads to marked kinetic ef- fects that could be explained by an augmented closed-state inactivation. Our data suggest that DPPX proteins are integral components of KO2 currents, and that their association with Kv4 subunits modulate the pharmacological profile of the heteromultimers.
PB Rockefeller University Press
SN 0022-1295
YR 2008
FD 2008
LK http://uvadoc.uva.es/handle/10324/29173
UL http://uvadoc.uva.es/handle/10324/29173
LA eng
NO The Journal of General Physiology, April 2008, vol. 131, n. 5. p. 455-471
NO Producción Científica
DS UVaDOC
RD 01-may-2024