Inositol trisphosphate and cyclic adenosine diphosphate-ribose increase quantal transmitter release at frog motor nerve terminals: Possible involvement of smooth endoplasmic reticulum

The release of chemical transmitter from nerve terminals is critically depe ndent on a transient increase in intracellular Ca2+.(6,25) The increase in Ca2+ may be due to influx of Ca2+ from the extracellular fluid(15) or relea se of Ca2+ from intracellular stores such as mitochondria.(1,8,18) Whether Ca2+ utilized in transmitter release is liberated from organelles other tha n mitochondria is uncertain. Smooth endoplasmic reticulum is known to relea se Ca2+, e.g., on activation by inositol trisphosphate or cyclic adenosine diphosphateribose,(2) so the possibility exists that Ca2+ from this source may be involved in the events leading to exocytosis. We examined this hypot hesis by testing whether inositol trisphosphate and cyclic adenosine diphos phate-ribose modified transmitter release, We used liposomes to deliver the se agents into the cytoplasmic compartment and binomial analysis to determi ne their effects on the quantal components of transmitter release. Administ ration of inositol trisphosphate (10(-4) M) caused a rapid, 25% increase in the number of quanta released, This was due to an increase in the number o f functional release sites, as the other quantal parameters were unaffected . The effect was reversed with 40 min of wash. Virtually identical results were obtained with cyclic adenosine diphosphate-ribose (10(-4) M). Inositol trisphosphate caused a 10% increase in quantal size, whereas cyclic adenos ine diphosphate-ribose had no effect, The results suggest that quantal tran smitter release can be increased by Ca2+ released from smooth endoplasmic r eticulum upon stimulation by inositol trisphosphate or cyclic adenosine dip hosphate-ribose, This may involve priming of synaptic vesicles at the relea se sites or mobilization of vesicles to the active zone. Inositol trisphosp hate may have an additional action to increase the content of transmitter w ithin the vesicles, These findings raise the possibility of a role of endog enous inositol phosphate and smooth endoplasmic reticulum in the regulation of cytoplasmic Ca2+ and transmitter release, (C) 1999 IBRO. Published by E lsevier Science Ltd.