RT info:eu-repo/semantics/article
T1 Kvβ1.2 subunit coexpression in HEK293 cells confers O2 sensitivity to Kv4.2 but not to shaker channels
A1 Pérez García, María Teresa
A1 López López, José Ramón
A1 González, Constancio
K1 Hypoxia
K1 Hipoxia
K1 Potassium channels
K1 Canales de potasio
AB Voltage-gated K+ (KV) channels are protein complexes composed of ion-conducting integral membrane α subunits and cytoplasmic modulatory β subunits. The differential expression and association of α and β subunits seems to contribute significantly to the complexity and heterogeneity of KV channels in excitable cells, and their functional expression in heterologous systems provides a tool to study their regulation at a molecular level. Here, we have studied the effects of Kvβ1.2 coexpression on the properties of Shaker and Kv4.2 KV channel α subunits, which encode rapidly inactivating A-type K+ currents, in transfected HEK293 cells. We found that Kvβ1.2 functionally associates with these two α subunits, as well as with the endogenous KV channels of HEK293 cells, to modulate different properties of the heteromultimers. Kvβ1.2 accelerates the rate of inactivation of the Shaker currents, as previously described, increases significantly the amplitude of the endogenous currents, and confers sensitivity to redox modulation and hypoxia to Kv4.2 channels. Upon association with Kvβ1.2, Kv4.2 can be modified by DTT (1,4 dithiothreitol) and DTDP (2,2′-dithiodipyridine), which also modulate the low pO2 response of the Kv4.2+β channels. However, the physiological reducing agent GSH (reduced glutathione) did not mimic the effects of DTT. Finally, hypoxic inhibition of Kv4.2+β currents can be reverted by 70% in the presence of carbon monoxide and remains in cell-free patches, suggesting the presence of a hemoproteic O2 sensor in HEK293 cells and a membrane-delimited mechanism at the origin of hypoxic responses. We conclude that β subunits can modulate different properties upon association with different KV channel subfamilies; of potential relevance to understanding the molecular basis of low pO2 sensitivity in native tissues is the here described acquisition of the ability of Kv4.2+β channels to respond to hypoxia.
PB Rockefeller University Press
SN 0022-1295
YR 1999
FD 1999
LK http://uvadoc.uva.es/handle/10324/25919
UL http://uvadoc.uva.es/handle/10324/25919
LA eng
NO Journal of Genetic Physiology,1999, vol. 113. p. 897-907
NO Producción Científica
DS UVaDOC
RD 17-jul-2024