Angiotensin II Induces Automatic Activity of the Isolated Guinea Pig Pulmonary Vein Myocardium through Activation of the IP3 Receptor and the Na+-Ca2+ Exchanger

• Published in: International journal of molecular sciences Vol. 20; no. 7; p. 1768
• Main Authors: Tanaka, Yusuke, Obata, Kae, Ohmori, Tamano, Ishiwata, Kohei, Abe, Manato, Hamaguchi, Shogo, Namekata, Iyuki, Tanaka, Hikaru
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 10.04.2019; MDPI
• Subjects: Angiotensin; Angiotensin I; Angiotensin II; automaticity; Automation; Calcium (intracellular); Calcium ions; Calcium signalling; Cardiac arrhythmia; Cardiomyocytes; Cellular manufacture; Depolarization; Electrical stimuli; Enzymes; Extracellular matrix; Firing rate; Guinea pigs; Heart; Intracellular; Intracellular signalling; Ion currents; Myocardium; Na+/Ca2+ exchanger; pulmonary vein myocardium; Renin; Stimulation; Veins & arteries
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20071768

The automaticity of the pulmonary vein myocardium is known to be the major cause of atrial fibrillation. We examined the involvement of angiotensin II in the automatic activity of isolated guinea pig pulmonary vein preparations. In tissue preparations, application of angiotensin II induced an automatic contractile activity; this effect was mimicked by angiotensin I and blocked by losartan, but not by PD123,319 or carvedilol. In cardiomyocytes, application of angiotensin II induced an increase in the frequency of spontaneous Ca2+ sparks and the generation of Ca2+ transients; these effects were inhibited by losartan or xestospongin C. In tissue preparations, angiotensin II caused membrane potential oscillations, which lead to repetitive generation of action potentials. Angiotensin II increased the diastolic depolarization slope of the spontaneous or evoked action potentials. These effects of angiotensin II were inhibited by SEA0400. In tissue preparations showing spontaneous firing of action potentials, losartan, xestospongin C or SEA0400 decreased the slope of the diastolic depolarization and inhibited the firing of action potentials. In conclusion, in the guinea pig pulmonary vein myocardium, angiotensin II induces the generation of automatic activity through activation of the IP3 receptor and the Na+-Ca2+ exchanger.