α-LTX and α-LTXN4C induce [Ca2+]i elevation through different mechanisms in pancreatic β cells

α-latrotoxin (α-LTX), a neurotoxin from black-widow spider, causes vesicles release in presynapse of nerve terminal after binding to specific membrane receptors. α-LTXN4C is an effective tool binding to calcium independent receptor for latrotoxin (CIRL), which is used to elucidate the mechanism of receptor-mediated signal pathway. In our study on the pancreatic β cells, we found that α-LTX inserts into the plasma membrane and forms stable non-selective cation channels. The influx of extracellular Ca2+ through the channels causes massive Ca2+-dependent exocytosis of insulin-containing vesicles, whereas, α-LTXN4C, binding with its receptor CIRL in extracellular divalent cation-dependent way, increases Ca2+]i by mobilization of the intracellular calcium stores. These authors contributed equally to the work.