摘要
The present study attempted to test a novel hypothesis that Ca^2+ 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 Ca^2+ sparks, which could be reversed by ryanodine(10 μmol/L). Electrophysiological experiments revealed that tacrolimus(10 μmol/L) increased the large-conductance Ca^2+-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 Ca^2+ sparks released from ryanodine receptors, which inhibited the NE- or KCl-induced contraction in rat aorta.
The present study attempted to test a novel hypothesis that Ca^2+ 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 Ca^2+ sparks, which could be reversed by ryanodine(10 μmol/L). Electrophysiological experiments revealed that tacrolimus(10 μmol/L) increased the large-conductance Ca^2+-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 Ca^2+ sparks released from ryanodine receptors, which inhibited the NE- or KCl-induced contraction in rat aorta.
基金
supported by the National Natural Science Foundation of China(No.81102439)