抄録
IKs current modulation through stretch or swelling of single cells was reported, although exact mechanism of this regulation is still not clarified. It was demonstrated that AT1 receptor could be activated by stretch in the absence of angiotensin II. Therefore, we attempted to elucidate the involvement of AT1 receptor in swelling-activated IKs increase in guinea pig atrial myocytes by the whole-cell patch-clamp method. Hypotonic solution (HS) with osmolality 70% enhanced guinea pig atrial IKs tail current by 84% (n = 12). Pretreatment with specific AT1 receptor antagonist candesartan (1 or 5 μM) attenuated IKs increase to 48% (n = 10) and 43% (n = 9), respectively. IKs enhancement coincided with increase of the cells width by 19% (n = 12), which was completely reversible during readministration of isotonic solution and candesartan has no influence on the changes of cell dimensions. PLC inhibitor U73122 (3 μM) in the pipette solution or superfusion with PKC inhibitor BIS I (200 nM) did not affect the extent of IKs increase by HS. On the contrary, tyrosine kinase (TK) inhibitors A23 (20 μM) and A25 (20 μM) reduced IKs enhancement to 42 and 52%, respectively. Tyrosine phosphatase inactivation by orthovanadate (500 μM) loaded into the cells through the pipette solution stimulated IKs magnification to 124%. The above results suggest involvement of AT1 receptor and TKs in the swelling-activated IKs enhancement in guinea pig atrium. [J Physiol Sci. 2007;57 Suppl:S227]
