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Kv7.1/Kv7.5 heterotetramers with emerging properties on vascular smooth muscle physiology

AuthorsOliveras, Anna; Roura-Ferrer, Meritxell; Cruz, Alicia de la ; Prieto, Ángela ; Etxeberría, Ainhoa; Cogolludo, Angel; Valenzuela, Carmen ; Villarroel, Alvaro; Felipe, Antonio
Issue Date2014
Citation37th Congress of the Spanish Society of Physiological Sciences (2013)
Abstract[Introduction]: Voltage-dependent K+ channels from Kv7 (KCNQ) family have well-established physiological roles in cardiovascular and nervous system, although functions in blood vessels remain unclear. Evidence suggests that Kv7.1, Kv7.4 and Kv7.5 control vascular reactivity. However, because controversial pharmacological results Kv7.1 is under intense investigation. In this scenario, the ability of Kv7 channels to form heterotetramers is of physiological relevance. Thus, Kv7.4/Kv7.5 heterotetramers paves the way for novel interaction that could shed light to controversial pharmacological results. We aim whether Kv7.1 and Kv7.5 form heterotetramers increasing the diversity of channel responses in vascular smooth muscle. [Methods and Results]: We demonstrated Kv7.1/Kv7.5 structures in heterologous system by many different approaches, such as electrophysiology, coimmunoprecipitation and FRET. Heteromeric channels are retained at the endoplasmatic reticulum and, unlike Kv7.1 channels, heteromers localize out of lipid rafts. These results are supported by experiments in isolated smooth muscle myocytes. Kv7.1 and Kv7.5 are expressed in aorta, cava and coronary myocytes. Electrophysiological and miography recordings using linopiridine, chromanol 293B and retigabine support Kv7.1/Kv7.5 heterotetramers that co-immunoprecipitation experiments further confirmed. Finally, lipid raft isolation from different tissues corroborated that expression of Kv7.5 releases Kv7.1/Kv7.5 channels out of raft structures. [Discussion]: Kv7.1 and Kv7.5 are differentially expressed in blood vessels where they contribute to control vascular reactivity. We prove that they do heterotetramerize increasing the diversity of their physiological response. These data may help to better understand the scenario of Kv7 channels and vascular physiology.
DescriptionResumen del trabajo presentado al 37th Congress of the Spanish Society of Physiological Sciences (SECF), celebrado del 24 al 26 de Septiembre de 2014 en Granada (España):-- et al.
Appears in Collections:(IIBM) Comunicaciones congresos
(UBF) Comunicaciones congresos
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