REGULATION OF THE CA2+ SENSITIVITY OF EXOCYTOSIS BY RAB3A

Ca2+ ions trigger the release of hormones and neurotransmitters and co ntribute to making the secretory vesicles competent for fusion. Here, we present evidence for the involvement of the GTP-binding protein Rab 3a in the sensitivity of the exocytotic process to internal [Ca2+]. Th e secretory activity of bovine adrenal chromaffin cells was elicited b y Ca2+ dialysis through a patch-clamp pipette and assayed by monitorin g changes in cell membrane capacitance. Microinjection of antisense ol igonucleotides directed to rab3a mRNA increased the secretory activity observed at low (0.2-4 mu M) [Ca2+], but did not change the maximal a ctivity observed at 10 mu M free [Ca2+]. Moreover, after a train of de polarizing stimuli, the secretory activity of antisense-injected cells dialyzed with 10 mu M [Ca2+] was increased significantly compared wit h that of control cells. This result suggests that the activity of eit her Rab3a or its partners might change upon stimulation. We conclude t hat Rab3a, together with its partners, participates in the Ca2+ depend ence of exocytosis and that its activity is modulated further in a sti mulus-dependent manner. These findings should provide some clues to el ucidate the role of Rab3a in synaptic plasticity.