Arrhythmias, elicited by catecholamines and serotonin, vanish in human chronic atrial fibrillation

Abstract

Fig. 1. Bone cells express Avprs. Immunofluorescence micrographs (A) and Western immunoblotting (B)show the expression of Avpr1α in osteoblasts and osteoclasts, and as a function of osteoblast (mineralization) and osteoclast (with Rankl) differentiation. The expression of Avp (ligand) and Avpr1α (receptor) in osteoblasts is regulated by 17β-estradiol, as determined by quantitative PCR (C) and Western immunoblotting (D). (Magnification: A, 63×.) Because Avp is a small peptide, its precursor neurophysin II is measured. Statistics: Student t test, P values shown compared with 0 h. Stimulation of Erk phosphorylation (p-Erk) as a function of total Erk (t-Erk) by Avp (10 −8 M) in osteoclast precursors (preosteoclasts), osteoclasts (OC), and osteoblasts establishes functionality of the Avpr1α in the presence or absence of the receptor inhibitor SR49059 (10 −8 M) (E). Western immunoblotting showing the expression of Avpr2 in preosteoclasts, OCs (F), and osteoblasts (G) isolated from Avpr1α −/− mice, as well as in MC3T3.E1 osteoblast precursors (G). Functionality of Avpr2 was confirmed by the demonstration that cells from Avpr1α −/− mice remained responsive to AVP in reducing the expression of osteoblast differentiation genes, namely Runx2, Osx, Bsp, Atf4, Opn, and Osteocalcin (quantitative PCR, P values shown) (H). Only relevant bands from Western blots are shown, with gaps introduced where empty lanes are excised to conserve space.

Tachycardia-induced silencing of subcellular Ca2+ signaling in atrial myocytes

“…atrial trabeculae from patients with persistent AF compared with patients with sinus rhythm (48,49). Consistent with the concept of Ca 2+ signaling silencing, lone rapid atrial pacing or experimental AF as such has never been shown to produce an enhanced rate of atrial ectopic activity, nor has spontaneous recurrence of AF been documented, even after prolonged periods of AF (10).…”

“…In some AF patients, in whom spontaneous ectopic activity in isolated trabeculae was reduced, the effects of Ca 2+ signaling silencing appear to prevail (48,49).…”

2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS

“…Hiperfosforylacja różnych białek uczestniczących w gospodarce jonów wapniowych może się przyczyniać do zwiększenia incydentów samoistnego uwalniania jonów wapnia oraz wyzwalanej aktywności [97,98], wywołując w ten sposób ektopię i sprzyjając AF. Mimo że koncepcję niestabilności gospodarki jonów wapniowych ostatnio zakwestionowano [106,107], to czynnik ten może leżeć u podłoża AF w przedsionkach, które uległy przebudowie strukturalnej, i może tłumaczyć, w jaki sposób zmiany napięcia układu autonomicznego mogą generować AF [80,105].…”

2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS

“…96 Hyperphosphorylation of various Ca 2+ -handling proteins may contribute to enhanced spontaneous Ca 2+ release events and triggered activity, 97,98 thus causing ectopy and promoting AF. Although the concept of Ca 2+ -handling instability has been challenged recently, 106,107 it may mediate AF in structurally remodelled atria and explain how altered autonomic tone can generate AF. 80,105 …”