Role of ion channels in sepsis-induced atrial tachyarrhythmias in guinea pigs
Article first published online: 10 APR 2012
© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society
British Journal of Pharmacology
Special Issue: Themed Section: Secretin Family (Class B) G Protein-Coupled Receptors - from Molecular to Clinical Perspectives. Guest Editors: David R Poyner and Debbie L Hay
Volume 166, Issue 1, pages 390–400, May 2012
How to Cite
Aoki, Y., Hatakeyama, N., Yamamoto, S., Kinoshita, H., Matsuda, N., Hattori, Y. and Yamazaki, M. (2012), Role of ion channels in sepsis-induced atrial tachyarrhythmias in guinea pigs. British Journal of Pharmacology, 166: 390–400. doi: 10.1111/j.1476-5381.2011.01769.x
- Issue published online: 10 APR 2012
- Article first published online: 10 APR 2012
- Accepted manuscript online: 3 NOV 2011 05:13AM EST
- Received; 28 August 2011; Revised; 7 October 2011; Accepted; 27 October 2011
- action potential;
- atrial myocytes;
- inducible NOS (iNOS);
- ion channels;
BACKGROUND AND PURPOSE Supraventricular tachyarrhythmias, including atrial fibrillation, are occasionally observed in patients suffering from sepsis. Modulation of cardiac ion channel function and expression by sepsis may have a role in the genesis of tachyarrhythmias.
EXPERIMENTAL APPROACH Sepsis was induced by LPS (i.p.; 300 µg·kg−1) in guinea pigs. Membrane potentials and ionic currents were measured in atrial myocytes isolated from guinea pigs 10 h after LPS, using whole cell patch-clamp methods.
KEY RESULTS In atrial cells from LPS-treated animals, action potential duration (APD) was significantly shortened. It was associated with a reduced L-type Ca2+ current and an increased delayed rectifier K+ current. These electrophysiological changes were eliminated when NG-nitro-l-arginine methyl ester (l-NAME) or S-ethylisothiourea was given together with LPS. In atrial tissues from LPS-treated animals, Ca2+ channel subunits (Cav1.2 and Cav1.3) decreased and delayed rectifier K+ channel subunits (Kv11.1 and Kv7.1) increased. However, L-NAME treatment did not substantially reverse such changes in atrial expression in LPS-treated animals, with the exception that Kv11.1 subunits returned to control levels. After LPS injection, inducible NOS in atrial tissues was up-regulated, and atrial NO production clearly increased.
CONCLUSIONS AND IMPLICATIONS In atrial myocytes from guinea pigs with sepsis, APD was significantly shortened. This may reflect nitration of the ion channels which would alter channel functions, rather than changes in atrial expression of the channels. Shortening of APD could serve as one of the mechanisms underlying atrial tachyarrhythmia in sepsis.