Sulfur Dioxide Derivative Prevents the Prolongation of Action Potential During the Isoproterenol-Induced Hypertrophy of Rat Cardiomyocytes

Uğur Dalaman,Ahmed K Sircan,Sevgi A Şengül,Hasan Özdoğan,Nazmi Yaraş

doi:10.1590/0001-3765202120201664

Uğur Dalaman, Ahmed K Sircan + Show 3 more

Open Access

https://doi.org/10.1590/0001-3765202120201664

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Abstract

Exogenous SO2 is toxic especially to the pulmonary and cardiovascular system, similar to nitric-oxide, carbon-monoxide, and hydrogen-sulfide. Endogenous SO2 is produced in many cell types. The SO2 content of the rat heart has been observed to substantially decrease during isoproterenol-induced hypertrophy. This study sought to determine whether an SO2 derivative could inhibit the prolongation of action potentials during the isoproterenol-induced hypertrophy of rat cardiomyocytes and explore the ionic currents. Alongside electrocardiogram recordings, the voltage and current-clamped measurements were conducted in the enzymatically isolated left ventricular cardiomyocytes of Wistar rats. The consistency of the results was evaluated by the novel mathematical electrophysiology model. Our results show that SO2 significantly blocked the prolongation of QT-interval and action potential duration. Furthermore, SO2 did not substantially affect the Na+ currents and did not improve the decreased steady-state and transient outward K+ currents, but it reverted the reduced L-type Ca2+ currents (I CaL) to the physiological levels. Altered inactivation of I CaL was remarkably recovered by SO2. Interestingly, SO2 significantly increased the Ca2+ transients in hypertrophic rat hearts. Our mathematical model also confirmed the mechanism of the SO2 effect. Our findings suggest that the shortening mechanism of SO2 is related to the Ca2+ dependent inactivation kinetics of the Ca2+ current.

Highlights

Sulfur dioxide (SO2) is an air pollutant and a toxic agent that has been reported to be harmful to many organs including the heart, liver, and brain (Meng 2003, Meng & Liu 2007)
We evaluated the heart weight to tibia length (HW/ TL) ratio, which was not affected by changes in BW during the experimental period
We found that isoproterenol administration lowers the fast inactivation constant at 0 mV compared to the Control group (Figure 4e)

Summary

Introduction

Sulfur dioxide (SO2) is an air pollutant and a toxic agent that has been reported to be harmful to many organs including the heart, liver, and brain (Meng 2003, Meng & Liu 2007). SO2 can be generated from the metabolism of sulfur-containing amino acids (Stipanuk 2004, Du et al 2008, Luo et al 2011), and this endogenous compound and its derivatives can alleviate various cardiovascular diseases in mammals (Jin et al 2008, Liang et al 2011, Zhang et al 2011). Cysteine dioxygenase (CDO) catalyzes L-cysteine, a sulfur-containing amino acid, into L-cysteinesulfinate, which is converted by aspartate aminotransferase (AAT) to β-sulfinylpyruvate, which subsequently breaks down into pyruvate and SO2 (Stipanuk 1986). Gasotransmitters such as carbon monoxide (CO), nitric oxide (NO), and hydrogen sulfide

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