ABSTRACT
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.
Subject(s)
Animals , Male , Rats , Aorta , Cell Biology , Metabolism , Physiology , Calcium Signaling , Cells, Cultured , Large-Conductance Calcium-Activated Potassium Channels , Metabolism , Muscle, Smooth, Vascular , Metabolism , Physiology , Myocytes, Smooth Muscle , Metabolism , Norepinephrine , Pharmacology , Rats, Sprague-Dawley , Ryanodine , Pharmacology , Tacrolimus , Pharmacology , VasoconstrictionABSTRACT
In cardiac myocytes, Ca2+ sparks origining from a single RyR or a few RyRs are triggered by a single L-type Ca2+ channel or occur spontaneously. Ca2+ sparks constitute the elementary local Ca 2+ release events from the SR. Ca2+ sparks occur at Z-lines and randomly distribute at different locations, the characteristics of the kinetics are regulated by many factors. In addition, ICa.T, Na+/Ca2+ exchange, ICa (TTX) and IP3 are other putative sources of Ca2+ that trigger SR Ca2+ release.
ABSTRACT
Fluorescence probe Fluo-3AM can be luminary in confocal microscope after combining Ca2+,So nomadic Ca2+ in cytoplasm can be measured and tested by this way.Some confocal laser scan images are obtained after calcium in muscle fibers signed with F1uo-3AM. Then mapping function is used to convert the gray level image into colorful image by pseudo-color enhancement theory in digital image.Compared to the original gray level image,the processed pseudo-color image could be more easily distinguished.So the methods had a great value in Ca2+ detection fields.
ABSTRACT
In cardiac myocytes, Ca 2+ sparks origining fr om a single RyR or a few RyRs are triggered by a single L-type Ca 2+ channel or occur spontaneously. Ca 2+ sparks constitute the elementary local Ca 2+ release events from the SR. Ca 2+ sparks occur at Z-lines and rando mly distribute at different locations, the characteristics of the kinetics are r egulated by many factors. In addition, I Ca.T, Na+/Ca 2+ exchang e, I Ca(TTX) and IP 3 are other putative sources of Ca 2+ that tr igger SR Ca 2+ release.