Journal
BRITISH JOURNAL OF PHARMACOLOGY
Volume 166, Issue 1, Pages 390-400Publisher
WILEY
DOI: 10.1111/j.1476-5381.2011.01769.x
Keywords
action potential; atrial myocytes; inducible NOS (iNOS); ion channels; NO; polyphenol; sepsis
Categories
Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Grants-in-Aid for Scientific Research [21592001] Funding Source: KAKEN
Ask authors/readers for more resources
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 mu g.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 N-G-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 (Ca(v)1.2 and Ca(v)1.3) decreased and delayed rectifier K+ channel subunits (K(v)11.1 and K(v)7.1) increased. However, L-NAME treatment did not substantially reverse such changes in atrial expression in LPS-treated animals, with the exception that K(v)11.1 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available