SYNERGISM BETWEEN HYPOTONICALLY INDUCED CALCIUM-RELEASE AND FATTY ACYL-COA ESTERS INDUCED CALCIUM-RELEASE FROM INTRACELLULAR STORES

The non-mitochondrial Ca2+ stores in permeabilized A7r5 cells responde d to a decrease in Mg-ATP concentration with a pronounced Ca2+ release if 20 mu M CoA was present. This release was rather specific for the preincubation or removal of ATP. ATP gamma S was much less effective a nd AMP-PNP, GTP, ITP, CTP, UTP, ADP, AMP, adenosine and adenine had no effect. CoA activated with an EC50 of 6 mu M. Dephospho-CoA was a les s effective cofactor and desulfo-CoA was ineffective. The release indu ced by Mg-ATP removal did not occur in the presence of 2% fatty acid-f ree bovine serum albumin and did not develop at 4 degrees C. All these findings suggest that CoA had to be acylated by endogenous fatty-acyl -CoA synthetase to become effective. Myristoyl-and palmitoyl-CoA ester s were identified as the most effective cofactors for the release. Ca2 + release induced by removing Mg-ATP did not occur if the osmolality o f the medium was kept constant by addition of mannitol, sucrose, KCl, MgCl2 or Mg-GTP, indicating that the decrease in tonicity was the trig ger for the release. Mg-ATP plus CoA also synergized with Ca2+ release induced by a hypotonic shock imposed by diluting the medium with H2O. Osmolality changes induced by decreasing the Mg-ATP concentration wer e more effective in releasing Ca2+ than equal decreases in concentrati on of all solutes. We conclude that fatty acyl-CoA esters sensitize th e hypotonically induced Ca2+ release from the non-mitochondrial Ca2+ s tores.