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 microM 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 microM, 50 microM and 100 microM decreased 45Ca2+ retention in permeabilized hepatocytes. This inhibition of Ca2+ retention by ryanodine was not due to inhibition of the microsomal Ca(2+)-ATPase. Dantrolene, a compound shown previously to inhibit ryanodine binding in the liver, also decreased 45Ca2+ 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 Ca(2+)-release channel in liver is discussed.
Bazotte
R B
RB
Department of Physiology and Cell Biology, University of Texas Medical School, Houston 77225.
Pereira
B
B
Higham
S
S
Shoshan-Barmatz
V
V
Kraus-Friedmann
N
N
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002478:Cells, Cultured; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D003620:Dantrolene / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016257:Fura-2; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D012433:Ryanodine / Q000494:pharmacology*; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism
D015220:Calcium Channels; D012433:Ryanodine; D000252:Calcium-Transporting ATPases; D003620:Dantrolene; D016257:Fura-2