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- Title
Angiotensin II type 1 receptor mediates partially hyposmotic-induced increase of I<sub>Ks</sub> current in guinea pig atrium.
- Authors
Zankov, Dimitar P.; Toyoda, Futoshi; Omatsu-Kanbe, Mariko; Matsuura, Hiroshi; Horie, Minoru
- Abstract
A repolarizing conduction in the heart augmented by hyposmotic or mechanically induced membrane stretch is the slow component of delayed rectifier K+ current ( IKs). IKs upregulation is recognized as a factor promoting appearance of atrial fibrillation (AF) since gain-of-function mutations of the channel genes have been detected in congenital AF. Mechanical stretch activates angiotensin II type 1 (AT1) receptor in the absence of its physiological ligand angiotensin II. We investigated the functional role of AT1 receptor in IKs enhancement in hyposmotically challenged guinea pig atrial myocytes using the whole-cell patch-clamp method. In atrial myocytes exposed to hyposmotic solution with osmolality decreased to 70% of the physiological level, IKs was enhanced by 84.1%, the duration of action potential at 90% repolarization (APD90) was decreased by 16.8%, and resting membrane potential was depolarized (+4.9 mV). The hyposmotic-induced effects on IKs and APD90 were significantly attenuated by specific AT1 receptor antagonist candesartan (1 and 5 μM). Pretreatment of atrial myocytes with protein tyrosine kinase inhibitors tyrphostin A23 and A25 suppressed but the presence of tyrosine phosphatase inhibitor orthovanadate augmented hyposmotic stimulation of IKs. The above results implicate AT1 receptor and tyrosine kinases in the hyposmotic modulation of atrial IKs and suggest acute antiarrhythmic properties of AT1 antagonists in the settings of stretch-related atrial tachyarrhythmias.
- Subjects
ANGIOTENSIN I; ANGIOTENSIN II; RECEPTOR antibodies; BIOLOGICAL membranes; ATRIAL fibrillation; PROTEIN-tyrosine kinases; AMINO acids
- Publication
Pflügers Archiv: European Journal of Physiology, 2009, Vol 458, Issue 5, p837
- ISSN
0031-6768
- Publication type
Article
- DOI
10.1007/s00424-009-0669-8