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Angiotensin II type 1 receptor mediates partially hyposmotic-induced increase of I Ks current in guinea pig atrium

  • Ion Channels, Receptors and Transporters
  • Published:
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Abstract

A repolarizing conduction in the heart augmented by hyposmotic or mechanically induced membrane stretch is the slow component of delayed rectifier K+ current (I Ks). I Ks 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 I Ks 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, I Ks 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 I Ks 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 I Ks. The above results implicate AT1 receptor and tyrosine kinases in the hyposmotic modulation of atrial I Ks and suggest acute antiarrhythmic properties of AT1 antagonists in the settings of stretch-related atrial tachyarrhythmias.

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Acknowledgments

This study was supported by Japanese Society for the Promotion of Science, research grant no 19-07209.

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The authors have no potential conflict of interests.

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Authors and Affiliations

  1. Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Otsu, Shiga, 520-2192, Japan

    Dimitar P. Zankov & Minoru Horie

  2. Department of Physiology, Shiga University of Medical Science, Otsu, Shiga, 520-2192, Japan

    Futoshi Toyoda, Mariko Omatsu-Kanbe & Hiroshi Matsuura

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  1. Dimitar P. Zankov
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  2. Futoshi Toyoda
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Correspondence to Minoru Horie.

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Zankov, D.P., Toyoda, F., Omatsu-Kanbe, M. et al. Angiotensin II type 1 receptor mediates partially hyposmotic-induced increase of I Ks current in guinea pig atrium. Pflugers Arch - Eur J Physiol 458, 837–849 (2009). https://doi.org/10.1007/s00424-009-0669-8

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  • DOI: https://doi.org/10.1007/s00424-009-0669-8

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