INTRACELLULAR ADP MODULATES THE CA2-ACTIVATED CA2+ CURRENT IN A TEMPERATURE-DEPENDENT AND CA2+-DEPENDENT WAY( RELEASE)

The rat basophilic cell line RBL-1 is known to express high levels of the Ca2+ current activated by store depletion, known as Ca2+ release-a ctivated Ca2+ current (I-CRAC), the main Ca2+ influx pathway so far id entified in nonexcitable cells. We show here that, as reported in othe r cell types, metabolic drugs strongly inhibit the Ca2+ influx operate d by store depletion in RBL-1 cells also. We have tested the hypothesi s that intracellular adenine and/or guanine nucleotide levels act as c oupling factors between I-CRAC and eel metabolism. Using the whole cel l configuration of the patch-clamp technique, we demonstrate that addi tion of ADP to the intracellular solution significantly reduces I-CRAC induced by inositol 1,4,5-trisphosphate. This phenomenon differs from other regulatory pathways of I-CRAC since it is highly temperature-de pendent, is observable only in the presence of low intracellular Ca2buffering capacity, and requires a cytosolic factor(s) which is rapidl y lost during cell dialysis, Moreover, the inhibition is specific for ADP and is partially mimicked by ADP beta S and AMP, but not by GDP or GTP.