Positive Inotropic Effects of ATP Released via the Maxi-Anion Channel in Langendorff-Perfused Mouse Hearts Subjected to Ischemia-Reperfusion

Hiroshi Matsuura; Akiko Kojima; Yutaka Fukushima; Yu Xie; Xinya Mi; Ravshan Z Sabirov; Yasunobu Okada

doi:10.3389/fcell.2021.597997

Positive Inotropic Effects of ATP Released via the Maxi-Anion Channel in Langendorff-Perfused Mouse Hearts Subjected to Ischemia-Reperfusion

Front Cell Dev Biol. 2021 Jan 21:9:597997. doi: 10.3389/fcell.2021.597997. eCollection 2021.

Authors

Hiroshi Matsuura¹, Akiko Kojima², Yutaka Fukushima², Yu Xie¹, Xinya Mi¹, Ravshan Z Sabirov³, Yasunobu Okada^{4

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Affiliations

¹ Department of Physiology, Shiga University of Medical Science, Otsu, Japan.
² Department of Anesthesiology, Shiga University of Medical Science, Otsu, Japan.
³ Institute of Biophysics and Biochemistry, National University of Uzbekistan, Tashkent, Uzbekistan.
⁴ National Institute for Physiological Sciences (NIPS), Okazaki, Japan.
⁵ Department of Physiology, School of Medicine, Aichi Medical University, Nagakute, Japan.
⁶ Department of Physiology, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Abstract

The organic anion transporter SLCO2A1 constitutes an essential core component of the ATP-conductive large-conductance anion (Maxi-Cl) channel. Our previous experiments using Langendorff-perfused mouse hearts showed that the Maxi-Cl channel contributes largely to the release of ATP into the coronary effluent observed during 10-min reperfusion following a short period (6 min) of oxygen-glucose deprivation. The present study examined the effect of endogenous ATP released via Maxi-Cl channels on the left ventricular contractile function of Langendorff-perfused mouse hearts, using a fluid-filled balloon connected to a pressure transducer. After the initial 30-min stabilization period, the heart was then perfused with oxygen-glucose-deprived Tyrode solution for 6 min, which was followed by a 10-min perfusion with oxygenated normal Tyrode solution in the absence and presence of an ATP-hydrolyzing enzyme, apyrase, and/or an adenosine A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). In the absence of apyrase and DPCPX, the left ventricular developed pressure (LVDP) decreased from a baseline value of 72.3 ± 7.1 to 57.5 ± 5.5 mmHg (n = 4) at the end of 6-min perfusion with oxygen-glucose-deprived Tyrode solution, which was followed by a transient increase to 108.5 ± 16.5 mmHg during subsequent perfusion with oxygenated normal Tyrode solution. However, in the presence of apyrase and DPCPX, the LVDP decreased to the same degree during 6-min perfusion with oxygen-glucose-deprived Tyrode solution, but failed to exhibit a transient increase during a subsequent perfusion with oxygenated normal Tyrode solution. These results strongly suggest that endogenous ATP released through Maxi-Cl channels contributes to the development of transient positive inotropy observed during reperfusion after short-period hypoxia/ischemia in the heart.

Keywords: ATP release; Langendorff perfusion; endogenous ATP; ischemia-reperfusion; left ventricular contractile function; maxi-anion channel; mouse heart.