Open AccessCaveolin-3 is required for regulation of transient outward potassium current by angiotensin II in mouse atrial myocytes
Author(s) -
Leonid Tyan,
Daniel Turner,
Karlie R Komp,
Roman Y. Medvedev,
Evi Lim,
Alexey V. Glukhov
Publication year - 2021
Publication title -
american journal of physiology. heart and circulatory physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.524
H-Index - 197
eISSN - 1522-1539
pISSN - 0363-6135
DOI - 10.1152/ajpheart.00569.2020
Subject(s) - angiotensin ii , caveolae , medicine , myocyte , losartan , cardiac transient outward potassium current , endocrinology , renin–angiotensin system , chemistry , caveolin , potassium channel , losartan potassium , angiotensin receptor , atrial myocytes , receptor , microbiology and biotechnology , signal transduction , biology , patch clamp , blood pressure
Angiotensin II (AngII) is a key mediator of the renin-angiotensin system and plays an important role in the regulation of cardiac electrophysiology by affecting various cardiac ion currents, including transient outward potassium current, I to . AngII receptors and molecular components of I to , K v 4.2 and K v 4.3 channels, have been linked to caveolae structures. However, their functional interaction and the importance of such proximity within 50- to 100-nm caveolar nanodomains remain unknown. To address this, we studied the mechanisms of I to regulation by AngII in atrial myocytes of wild-type (WT) and cardiac-specific caveolin-3 (Cav3) conditional knockout (Cav3KO) mice. We showed that in WT atrial myocytes, a short-term (2 h) treatment with AngII (5 µM) significantly reduced I to density. This effect was prevented 1 ) by a 30-min pretreatment with a selective antagonist of AngII receptor 1 (Ang1R) losartan (2 µM) or 2 ) by a selective inhibition of protein kinase C (PKC) by BIM1 (10 µM). The effect of AngII on I to was completely abolished in Cav3-KO mice, with no change in a baseline I to current density. In WT atria, Ang1Rs co-localized with Cav3, and the expression of Ang1Rs was significantly decreased in Cav3KO in comparison with WT mice, whereas no change in K v 4.2 and K v 4.3 protein expression was observed. Overall, our findings demonstrate that Cav3 is involved in the regulation of Ang1R expression and is required for the modulation of I to by AngII in mouse atrial myocytes. NEW & NOTEWORTHY Angiotensin II receptor 1 is associated with caveolae and caveolar scaffolding protein caveolin-3 in mouse atrial myocytes that is required for the regulation of I to by angiotensin II. Downregulation of caveolae/caveolin-3 disrupts this regulation and may be implicated in pathophysiological atrial remodeling.