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Am J Physiol Heart Circ Physiol 273: H1745-H1753, 1997;
0363-6135/97 $5.00
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Vol. 273, Issue 4, H1745-H1753, October 1997

Dual effects of endothelins on the muscarinic K+ current in guinea pig atrial cells

Hiroshi Yamaguchi, Naoya Sakamoto, Yasuhide Watanabe, Toshihiro Saito, Yoshiaki Masuda, and Haruaki Nakaya

Department of Pharmacology and Third Department of Internal Medicine, Chiba University School of Medicine, Chiba 260, Japan

Effects of endothelins (ETs) on the acetylcholine receptor-operated K+ current (IK ACh) were examined in isolated guinea pig atrial cells using patch-clamp techniques. ET-1 or ET-3 produced a transient activation of IK ACh in atrial cells held at -40 mV. When IK ACh was preactivated by 1 µM carbachol, however, both ETs produced a transient potentiation followed by a sustained inhibition of the current. When IK ACh was maximally activated by 10 µM carbachol or 100 µM adenosine, these ETs produced only a sustained inhibition of the IK ACh. Their inhibitory effects on the preactivated IK ACh were concentration dependent, and the half-maximal effective concentrations were 314 pM for ET-1 and 1.13 nM for ET-3. The inhibitory effect of ET-1 was antagonized by BQ-485, a specific ETA receptor antagonist, but not by BQ-788, a specific ETB receptor antagonist, indicating that the ET-1 effect is mediated by ETA receptors. On the other hand, the inhibitory effect of ET-3 was antagonized by BQ-788 and more effectively by BQ-485, suggesting the involvement of "atypical" ET receptors. Both ETs partly reversed the carbachol-induced shortening of the action potential recorded in the current-clamp mode. Inhibitory effects of ET-1 and ET-3 on the preactivated IK ACh may contribute to the positive inotropic and chronotropic effects of ETs in atrial tissues.

inositol 1,4,5-trisphosphate; protein kinase C; action potential; patch clamp


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