AJP - Heart Calcium Transients and Cell-Sarcomere
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Am J Physiol Heart Circ Physiol 281: H596-H605, 2001;
0363-6135/01 $5.00
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Vol. 281, Issue 2, H596-H605, August 2001

Inotropic response of rabbit ventricular myocytes to endothelin-1: difference from isolated papillary muscles

M. A. Hassan Talukder, Ikuo Norota, Kiyoharu Sakurai, and Masao Endoh

Department of Pharmacology, Yamagata University School of Medicine, Yamagata 990-9585, Japan

Endothelin-1 (ET-1) increased cell shortening and Ca2+ transients over the concentration of 3 × 10-11 M to 10-9 M with EC50 of 8.3 × 10-11 M in rabbit single ventricular myocytes. Thus ET-1 was approximately 60 times more potent in single myocytes than in papillary muscles (EC50 = 5.1 × 10-9 M) of the same species. In single myocytes, ET-1 at 10-8 M elicited an inhibitory response that counteracted the facilitatory response: the concentration-response curve (CRC) for ET-1 was bell shaped. The ETA-receptor antagonist BQ-485 shifted CRC for ET-1 to the right in parallel; however, the facilitatory response to 10-8 M ET-1 was markedly enhanced by BQ-485 and also by the ETB antagonist BQ-788. The ETA/ETB antagonist TAK-044 abolished the ET-1-induced response. These findings indicate that the response to ET-1 of single myocytes is different from that of papillary muscles in concentration dependence, characteristics of the response, and susceptibility to ET-receptor antagonists. Anomalous pharmacological characteristics of ET-1-induced response in rabbit papillary muscles may be due to integrated regulatory mechanisms that may involve also various types of noncardiac cell in ventricular myocardium.

adult rabbit cardiomyocytes; cell shortening; Ca2+ transients; ETA receptor; ETB receptor


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