[Disturbances in the function of cardiomyocyte ryanodine receptors of spontaneously hypertensive rats revealed by 4-chloro-m-cresol].
The rates of Ca2+ release from sarcoplasmic reticulum in response to the activation of ryanodine receptors by 4-chloro-m-cresol in cardiomyocytes of three rat lines: spontaneously hypertensive (SHR) and normotensive WKY, and Wistar rats during five weeks of their growth and development have been studied to reveal differences in the function of ryanodine receptors at different stages of hypertension. Whereas the efflux of Ca2+ from sarcoplasmic reticulum in Wistar and WKY rat cardiomyocytes decreased in response to 4-chloro-m-cresol, an abrupt rise in the rate of [Ca2+]i increase was observed in myocytes of spontaneously hypertensive rats after 17 days of development. A correlation between this phenomenon and the occurrence of genetic defect of ryanodine receptors in SHR seems improbable because we did not register any differences in the rates of Ca2+ release from sarcoplasmic reticulum by the action of 4-chloro-m-cresol in concentrations 0.5-2.0 mM in the cardiomyocytes of newborn WKY and spontaneously hypertensive rats. On the other hand, pathological changes in the function of ryanodine receptors may become apparent later during ontogenesis. The connection of this phenomenon with an increase in the role of ryanodine receptors during the excitation-contraction coupling in muscle cell and an increase in the calpain expression by the age of 3 weeks in spontaneously hypertensive, but not in WKY rats, is discussed. It is supposed that the disintegration of the subunit of ryanodine receptors by calpain notably intensifies the Ca2+ release from sarcoplasmic reticulum after the activation of ryanodine receptors without affecting the characteristics of receptor binding.
Belostotskaia
G B
GB
Zakharov
E A
EA
Kliueva
N Z
NZ
Petrova
E I
EI
Nasledov
G A
GA
D000367:Age Factors; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002478:Cells, Cultured; D003408:Cresols / Q000494:pharmacology*; D066298:In Vitro Techniques; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology*; D013045:Species Specificity
D002120:Calcium Channel Agonists; D003408:Cresols; D019837:Ryanodine Receptor Calcium Release Channel; C006984:chlorocresol; D002118:Calcium