Effect of intermittent and continuous hypoxia on ryanodine receptors of rat heart.
Intermittent hypoxia (IH) adaptation has been shown to exert beneficial effects on the functions of hearts that had been subjected to insult by ischemia or ischemia/reperfusion. To understand whether calcium release channels/ryanodine receptors (RyRs) were involved, the effects of IH and continuous hypoxia (CH) on [3H]ryanodine binding to homogenates of rat hearts were investigated. Similar studies were performed on rat skeletal muscle. The main results on cardiac muscle were as follows: 1) Ischemia for up to 45 min in normal rat hearts had no obvious effect on the equilibrium ryanodine binding constant (K(d)), while the maximum number of ryanodine binding sites (B(max)) was affected in a time-dependent manner. B(max) was significantly increased with 15 min ischemia, which then returned to control levels upon prolonging the ischemia to 30 min. After 45 min ischemia, a small decrease of B(max) was observed. 2) IH adaptation for up to 28 days did not change B(max), but a significant decrease of B(max) was apparent after longer IH adaptation or after CH exposure. Although B(max) was not altered by 30 min ischemia, 30 min reperfusion following 30 min ischemia induced an evident decrease of B(max). After either IH or CH adaptation, the ischemia/reperfusion- induced decrease of B(max) was abolished. 3) Several effects on K(d) of ischemia and ischemia/reperfusion, with and without IH or CH adaptation, were observed. The most distinct and consistent finding was that a clear increase of K(d) was induced by ischemia or ischemia/reperfusion in CH adapted rats. [3H]Ryanodine binding to homogenates of rat skeletal muscle was also affected by IH and CH adaptation. In contrast to that found in cardiac muscle, a decrease of B(max) in skeletal muscle appeared only after CH adaptation. The physiological significance of these effects is discussed.
Wang
Hui
H
Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
Zhu
Hai-Feng
HF
Xia
Ruohong
R
Zhou
Zhao-Nian
ZN
Zhu
Pei-Hong
PH
D000818:Animals; D001665:Binding Sites / Q000502:physiology; D000860:Hypoxia; D066298:In Vitro Techniques; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012433:Ryanodine / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D013997:Time Factors
D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine