Summary
The present study attempted to test a novel hypothesis that Ca2+ sparks play an important role in arterial relaxation induced by tacrolimus. Recorded with confocal laser scanning microscopy, tacrolimus (10 µmol/L) increased the frequency of Ca2+ sparks, which could be reversed by ryanodine (10 µmol/L). Electrophysiological experiments revealed that tacrolimus (10 µmol/L) increased the large-conductance Ca2+-activated K+ currents (BKCa) in rat aortic vascular smooth muscle cells (AVSMCs), which could be blocked by ryanodine (10 µmol/L). Furthermore, tacrolimus (10 and 50 µmol/L) reduced the contractile force induced by norepinephrine (NE) or KCl in aortic vascular smooth muscle in a concentration-dependent manner, which could be also significantly attenuated by iberiotoxin (100 nmol/L) and ryanodine (10 µmol/L) respectively. In conclusion, tacrolimus could indirectly activate BKCa currents by increasing Ca2+ sparks released from ryanodine receptors, which inhibited the NE- or KCl-induced contraction in rat aorta.
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This project was supported by the National Natural Science Foundation of China (No. 81102439).
Both authors contributed equally to this work.
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Chen, Yf., Wang, C., Zhang, R. et al. Tacrolimus inhibits vasoconstriction by increasing Ca2+ sparks in rat aorta. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 36, 8–13 (2016). https://doi.org/10.1007/s11596-016-1534-6
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DOI: https://doi.org/10.1007/s11596-016-1534-6