[Altered ryanodine receptor of rat cardiac sarcoplasmic reticulum and its underlying mechanism during septic shock].
The present study was undertaken to observe the changes of Ryanodine receptor of cardiac junctional sarcoplasmic reticulum (SR) in relation to membrane lipid microenvironment alteration during septic shock. The results showed that the Bmax for 3H-ryanodine binding to cardiac junctional SR was decreased by 41.3% (3.9 +/- 0.1 vs. sham 6.6 +/- 0.7 pmol/mg, P < 0.01) while the Kd value was unaffected during late septic shock (CLP 18 h). Ca2+ activated 3H-ryanodine binding significantly and reached a saturation value when Ca2+ concentration was 5 x 10(-5) mol/L, while the S0.5 and the Hill coefficient values remained unchanged during septic shock. Caffeine, ATP, and AMP-PCP activated while Mg2+, ruthenium red inhibited 3H-ryanodine binding in both groups but the A0.5 (concentration requires for half maximum activation) and the IC50 (concentration requires for half-maximum inhibition) for the above mentioned activators and inhibitors, were respectively unaffected during septic shock. Digestion of cardiac SR isolated from control rats with phospholipase A2 inhibited 3H-ryanodine binding, which could be dramatically recovered by the incorporation of phosphatidylcholine (PC), or phosphatidylserine (PS), or phosphatidylethanolamine (PE) into the isolated cardiac SR. Incorporation of above phospolipids into SR isolated from septic rats reversed shock-induced inhibition of 3H-ryanodine binding. It is concluded that the mechanism responsible for the inhibition of 3H-ryanodine binding of junctional SR during septic shock may be related to modification of membrane lipid microenvironment in response to PLA2 overactivation during septic shock.
D000818:Animals; D001693:Biological Transport, Active; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D019837:Ryanodine Receptor Calcium Release Channel; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D012772:Shock, Septic / Q000378:metabolism*
D015220:Calcium Channels; D008563:Membrane Lipids; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium