Some disturbances in the function of ryanodine receptors of spontaneously hypertensive rat cardiomyocytes detected using 4-chlorom-cresol

Abstract

The rate of Ca²⁺ release from the sarcoplasmic reticulum in response to the activation of ryanodine receptors with 4-chlorom-cresol in the cardiomyocytes of three rat strains—spontaneously hypertensive (SHR), normotensive (WKY), and Wistar rats—during 5 weeks of their growth and development was studied aiming to detect the functional differences in the operation of these receptors at various stages of arterial hypertension. In response to 4-chlorom-cresol, a drastic increase in the rates of [Ca²⁺]_i accumulation in SHR myocytes after 17 days of development is recorded versus a decrease in the rates of Ca²⁺ efflux from the sarcoplasmic reticulum of Wistar and WKY rat cardiomyocytes. A correlation between this phenomenon and a genetic defect of ryanodine receptors in SHR rats seems rather unlikely, as the newborn WKY and SHR rats exposed to 4-chlorom-cresol at a concentration range of 0.5–2.0 mM did not display any differences in the rate of sarcoplasmic reticulum Ca²⁺ release. On the other hand, it is possible that the pathological changes in the function of ryanodine receptors manifest themselves later in the ontogenesis. The connection of this phenomenon with an increase in the role of ryanodine receptors in the excitation-contraction coupling in muscle cells and an increase in the calpain expression in SHR rats (absent in the WKY rats) by the age of 3 weeks is discussed. It is assumed that the cleavage of ryanodine receptor subunits by calpain can noticeably intensify the sarcoplasmic reticulum Ca²⁺ release after activation of these receptors without influencing the receptor binding characteristics.