DPPX modifies TEA sensitivity of the Kv4 channels in rabbit carotid body chemoreceptor cells.
Chemoreceptor cells from rabbit carotid body (CB) exhibit transient outward currents reversibly inhibited by low P(o2). Molecular and functional dissection of the components of these outward currents indicates that at least two different channels (Kv4.3 and Kv3.4) contribute to this current. Furthermore, several lines of evidence support the conclusion that Kv4 channel subfamily members (either Kv4.3 alone or Kv4.3/Kv4.1 heteromultimers) are the oxygen sensitive K channels (K(o2)) in rabbit CB chemoreceptor cells. However, the pharmacological characterization of these currents shows that they are almost completely blocked by high external TEA concentrations, while Kv4 channels have been shown to be TEA-insensitive. We hypothesized that the expression of regulatory subunits in chemoreceptor cells could modify TEA sensitivity of Kv4 channels. Here, we explore the presence and functional contribution of DPPX to K(o2) currents in rabbit CB chemoreceptor cells by using DPPX functional knockdown with siRNA. Our data suggest that DPPX proteins are integral components of K(o2) currents, and that their association with Kv4 subunits modulate the pharmacological profile of the heteromultimers.
Colinas
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Departamento de Bioquímica y Biología Molecular y Fisiología e Instituto de Biología y Genética Molecular (IBGM), Universidad de Valladolid y Consejo Superior de Investigaciones Científicas (CSIC), 47003 Valladolid, Spain. olaiacm@ibgm.uva.es
Pérez-Carretero
F D
FD
Alonso
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E
López-López
J R
JR
Pérez-García
M T
MT
D000818:Animals; D001483:Base Sequence; D002344:Carotid Body / Q000187:drug effects* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D011817:Rabbits; D051672:Shal Potassium Channels / Q000378:metabolism*; D019789:Tetraethylammonium / Q000494:pharmacology*; D013997:Time Factors; D014970:Xanthines / Q000494:pharmacology*
D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051672:Shal Potassium Channels; D014970:Xanthines; D019789:Tetraethylammonium; C049140:1,3-dipropyl-8-phenylxanthine