α-latrotoxin (α-LTX), a neurotoxin from black-widow spider, causes vesicles release in pre- synapse 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 ex- tracellular 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. α-LTXN4C is an effective tool binding to calcium independent receptor for latrotoxin (CIRL), a neurotoxin from black-widow spider, causes vesicles release in pre- synapse of nerve terminal after binding to specific membrane receptors ), 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 ex- tracellular Ca2 + through the channels causes massive Ca2 + -dependent exocytosis of insulin-containing vesicles, but, α-LTXN4C, binding with its receptor CIRL in extracellular divalent cation-dependent way, increases [Ca2 +] i by mobilization of the intracellular calcium stores.