Τίτλος:
Desmin is essential for the structure and function of the sinoatrial node: implications for increased arrhythmogenesis
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Our objective was to investigate the effect of desmin depletion on the structure and function of the sinoatrial pacemaker complex (SANcl) and its implication in arrhythmogenesis. Analysis of mice and humans (SANcl) indicated that the sinoatrial node exhibits high amounts of desmin, desmoplakin, N-cadherin, and β-catenin in structures we call “lateral intercalated disks” connecting myocytes side by side. Examination of the SANcl from an arrhythmogenic cardiomyopathy model, desmin-deficient (Des-/-) mouse, by immunofluorescence, ultrastructural, and Western blot analysis showed that the number of these lateral intercalated disks was diminished. Also, electrophysiological recordings of the isolated compact sinoatrial node revealed increased pacemaker systolic potential and higher diastolic depolarization rate compared with wild-type mice. Prolonged interatrial conduction expressed as a longer P wave duration was also observed in Des-/mice. Upregulation of mRNA levels of both T-type Ca2+ current channels, Cav3.1 and Cav3.2, in the Des-/- myocardium (1.8- and 2.3-fold, respectively) and a 1.9-fold reduction of funny hyperpolarization-activated cyclic nucleotide-gated K+ channel 1 could underlie these functional differences. To investigate arrhythmogenicity, electrocardiographic analysis of Des-deficient mice revealed a major increase in supraventricular and ventricular ectopic beats compared with wild-type mice. Heart rate variability analysis indicated a sympathetic predominance in Des-/- mice, which may further contribute to arrhythmogenicity. In conclusion, our results indicate that desmin elimination leads to structural and functional abnormalities of the SANcl. These alterations may be enhanced by the sympathetic component of the cardiac autonomic nervous system, which is predominant in the desmin-deficient heart, thus leading to increased arrhythmogenesis. Copyright © 2020 the American Physiological Society
Συγγραφείς:
Mavroidis, M.
Athanasiadis, N.C.
Rigas, P.
Kostavasili, I.
Kloukina, I.
Te Rijdt, W.P.
Kavantzas, N.
Chaniotis, D.
Peter van Tintelen, J.
Skaliora, I.
Davos, C.H.
Περιοδικό:
American Journal of Physiology - Heart and Circulatory Physiology
Εκδότης:
American Physiological Society
Λέξεις-κλειδιά:
calcium channel T type; calcium channel T type Cav3.1; desmin; messenger RNA; unclassified drug; voltage gated calcium channel Cav3.2; Cacna1g protein, mouse; Cacna1h protein, mouse; calcium channel T type; desmin; Hcn1 protein, mouse; hyperpolarization activated cyclic nucleotide gated channel; potassium channel, adult; animal experiment; animal model; animal tissue; arrhythmogenesis; arrhythmogenic cardiomyopathy; Article; cardiac muscle cell; cardiomyopathy; controlled study; depolarization; diastolic depolarization rate; electrocardiography; electrophysiology; enzyme activation; female; heart rate variability; heart ventricle extrasystole; human; human cell; human tissue; hyperpolarization; immunofluorescence; male; mouse; nonhuman; priority journal; protein function; protein RNA binding; sinoatrial pacemaker complex; sinus node; supraventricular premature beat; upregulation; Western blotting; 129 mouse; action potential; adrenergic system; animal; biological rhythm; genetics; heart arrhythmia; heart rate; knockout mouse; metabolism; pathology; pathophysiology; sinus node; time factor; ultrastructure, Action Potentials; Adult; Animals; Arrhythmias, Cardiac; Biological Clocks; Calcium Channels, T-Type; Desmin; Female; Heart Rate; Humans; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; Male; Mice, 129 Strain; Mice, Knockout; Potassium Channels; Sinoatrial Node; Sympathetic Nervous System; Time Factors
DOI:
10.1152/ajpheart.00594.2019
