Altered parasympathetic nervous system regulation of the sinoatrial node in Akita diabetic mice

Journal of Molecular and Cellular Cardiology
Pooja S KrishnaswamyRobert A Rose

Abstract

Cardiovascular autonomic neuropathy (CAN) is a serious complication of diabetes mellitus that impairs autonomic regulation of heart rate (HR). This has been attributed to damage to the nerves that modulate spontaneous pacemaker activity in the sinoatrial node (SAN). Our objective was to test the hypothesis that impaired parasympathetic regulation of HR in diabetes is due to reduced responsiveness of the SAN to parasympathetic agonists. We used the Akita mouse model of type 1 diabetes to study the effects of the parasympathetic agonist carbachol (CCh) on SAN function using intracardiac programmed stimulation, high resolution optical mapping and patch-clamping of SAN myocytes. CCh decreased HR by 30% and increased corrected SAN recovery time (cSNRT) by 123% in wildtype mice. In contrast, CCh only decreased HR by 12%, and only increased cSNRT by 37% in Akita mice. These alterations were due to smaller effects of CCh on SAN electrical conduction and spontaneous action potential firing in isolated SAN myocytes. Voltage clamp experiments demonstrate that the acetylcholine-activated K(+) current (IKACh) is reduced in Akita SAN myocytes due to enhanced desensitization and faster deactivation kinetics. These IKACh alterations were norma...Continue Reading

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Citations

Sep 7, 2016·The Journal of Physiology·Motahareh MoghtadaeiRobert A Rose
Mar 16, 2017·Scientific Reports·Hailey J JansenRobert A Rose
Aug 1, 2015·Circulation. Arrhythmia and Electrophysiology·Rui HuaRobert A Rose
Jan 8, 2017·Arteriosclerosis, Thrombosis, and Vascular Biology·John N Stabley, Dwight A Towler
Mar 22, 2020·Proceedings of the National Academy of Sciences of the United States of America·Iuliia PolinaRobert A Rose
Jan 10, 2019·JACC. Basic to Translational Science·Martin MackaseyRobert A Rose
Feb 21, 2021·Clinical and Experimental Pharmacology & Physiology·Ahmed SultanFrank Christopher Howarth
Mar 17, 2021·Cardiovascular Research·Martin AguilarSvetlana Reilly
Jun 12, 2021·Heart Rhythm O2·Hailey J JansenRobert A Rose
Aug 1, 2021·Advanced Drug Delivery Reviews·Izabela Tuleta, Nikolaos G Frangogiannis
Aug 20, 2021·Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology·Laurent FauchierA John Camm

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