RT Journal Article
T1 Functional Assembly of Kv7.1/Kv7.5 Channels With Emerging Properties on Vascular Muscle Physiology
A1 Oliveras, Anna
A1 Roura Ferrer, Meritxell
A1 Solé, Laura
A1 Cruz, Alicia de la
A1 Prieto, Angela
A1 Etxebarria, Ainhoa
A1 Manils, Joan
A1 Morales Cano, Daniel
A1 Condom, Enric
A1 Soler, Concepció
A1 Cogolludo Torralba, Ángel Luis
A1 Valenzuela, Carmen
A1 Villarroel, Alvaro
A1 Comes, Núria
A1 Felipe, Antonio
AB Objective—Voltage-dependent K+ (Kv) channels from the Kv7 family are expressed in blood vessels and contribute to cardiovascular physiology. Although Kv7 channel blockers trigger muscle contractions, Kv7 activators act as vasorelaxants. Kv7.1 and Kv7.5 are expressed in many vessels. Kv7.1 is under intense investigation because Kv7.1 blockers fail to modulate smooth muscle reactivity. In this study, we analyzed whether Kv7.1 and Kv7.5 may form functional heterotetrameric channels increasing the channel diversity in vascular smooth muscles.Approach and Results—Kv7.1 and Kv7.5 currents elicited in arterial myocytes, oocyte, and mammalian expression systems suggest the formation of heterotetrameric complexes. Kv7.1/Kv7.5 heteromers, exhibiting different pharmacological characteristics, participate in the arterial tone. Kv7.1/Kv7.5 associations were confirmed by coimmunoprecipitation, fluorescence resonance energy transfer, and fluorescence recovery after photobleaching experiments. Kv7.1/Kv7.5 heterotetramers were highly retained at the endoplasmic reticulum. Studies in HEK-293 cells, heart, brain, and smooth and skeletal muscles demonstrated that the predominant presence of Kv7.5 stimulates release of Kv7.1/Kv7.5 oligomers out of lipid raft microdomains. Electrophysiological studies supported that KCNE1 and KCNE3 regulatory subunits further increased the channel diversity. Finally, the analysis of rat isolated myocytes and human blood vessels demonstrated that Kv7.1 and Kv7.5 exhibited a differential expression, which may lead to channel diversity.Conclusions—Kv7.1 and Kv7.5 form heterotetrameric channels increasing the diversity of structures which fine-tune blood vessel reactivity. Because the lipid raft localization of ion channels is crucial for cardiovascular physiology, Kv7.1/Kv7.5 heteromers provide efficient spatial and temporal regulation of smooth muscle function. Our results shed light on the debate about the contribution of Kv7 channels to vasoconstriction and hypertension.
PB American Heart Association
SN 1079-5642
SN 1524-4636
YR 2014
FD 2014-07
LK https://hdl.handle.net/20.500.14352/96920
UL https://hdl.handle.net/20.500.14352/96920
LA eng
NO Oliveras A, Roura-Ferrer M, Solé L, de la Cruz A, Prieto A, Etxebarria A, Manils J, Morales-Cano D, Condom E, Soler C, Cogolludo A, Valenzuela C, Villarroel A, Comes N, Felipe A. Functional assembly of Kv7.1/Kv7.5 channels with emerging properties on vascular muscle physiology. Arterioscler Thromb Vasc Biol. 2014 Jul;34(7):1522-30. doi: 10.1161/ATVBAHA.114.303801
DS Docta Complutense
RD 18 jul 2024