EFFECTS OF RYANODINE ON CALCIUM SEQUESTRATION IN THE RAT-LIVER

Ryanodine, a highly toxic alkaloid known to react specifically with the Ca2+ release channels in sarcoplasmic reticulum (SR), was employed to study Ca2+ sequestration in the liver. Ryanodine at a 200-mu-M concentration increased cytosolic free Ca2+ levels and phosphorylase a activity in isolated hepatocytes. These effects may involve microsomal Ca2+ sequestration, because ryanodine, in the presence of inhibitors of mitochondrial Ca2+ uptake, at Concentrations of 1 nM, 1-mu-M, 50-mu-M and 100-mu-M decreased Ca-45(2+) retention in permeabilized hepatocytes. This inhibition of Ca2+ retention by ryanodine was not due to inhibition of the microsomal Ca2+-ATPase. Dantrolene, a compound shown previously to inhibit ryanodine binding in the liver, also decreased Ca-45(2+) retention in permeabilized hepatocytes, and activated phosphorylase a. These results show that ryanodine administration alters calcium sequestration in liver. The possibility of the existence of a ryanodine-sensitive Ca2+-release channel in liver is discussed.