RT info:eu-repo/semantics/article
T1 KV1.5–KVβ1.3 Recycling Is PKC-Dependent
A1 Macias, Alvaro
A1 de la Cruz, Alicia
A1 Peraza, Diego A.
A1 Benito-Bueno, Angela de
A1 Gonzalez, Teresa
A1 Valenzuela, Carmen
AB KV1.5 channel function is modified by different regulatory subunits. KVβ1.3 subunits assemble with KV1.5 channels and induce a fast and incomplete inactivation. Inhibition of PKC abolishes the KVβ1.3-induced fast inactivation, decreases the amplitude of the current KV1.5-KVβ1.3 and modifies their pharmacology likely due to changes in the traffic of KV1.5-KVβ1.3 channels in a PKC-dependent manner. In order to analyze this hypothesis, HEK293 cells were transfected with KV1.5-KVβ1.3 channels, and currents were recorded by whole-cell configuration of the patch-clamp technique. The presence of KV1.5 in the membrane was analyzed by biotinylation techniques, live cell imaging and confocal microscopy approaches. PKC inhibition resulted in a decrease of 33 ± 7% of channels in the cell surface due to reduced recycling to the plasma membrane, as was confirmed by confocal microscopy. Live cell imaging indicated that PKC inhibition almost abolished the recycling of the KV1.5-KVβ1.3 channels, generating an accumulation of channels into the cytoplasm. All these results suggest that the trafficking regulation of KV1.5-KVβ1.3 channels is dependent on phosphorylation by PKC and, therefore, they could represent a clinically relevant issue, mainly in those diseases that exhibit modifications in PKC activity.
YR 2021
FD 2021
LK https://uvadoc.uva.es/handle/10324/66025
UL https://uvadoc.uva.es/handle/10324/66025
LA spa
NO Int J Mol Sci . 2021 Jan 29;22(3):1336. doi: 10.3390/ijms22031336
DS UVaDOC
RD 07-jun-2024