Carabelli V, Carra I, Carbone E
Department of Neuroscience, I.N.F.M. Research Unit, Turin, Italy.
Neuron. 1998 Jun;20(6):1255-68. doi: 10.1016/s0896-6273(00)80505-x.
In bovine chromaffin cells, the Ca2+ channels involved in exocytosis are effectively inhibited by ATP and opioids that are coreleased with catecholamines during cell activity. This autocrine loop causes a delay in Ca2+ channel activation that is quickly removed by preceding depolarizations. Changes in Ca2+ channel gating by secreted products thus make it possible to correlate Ca2+ channel activity to secretory events. Here, using cell-attached patch recordings, we found a remarkable correlation between delayed Ca2+ channel openings and neurotransmitter secretion induced by either local or whole-cell Ba2+ stimulation. The action is specific for N- and P/Q-type channels and largely prevented by PTX and mixtures of purinergic and opioid receptor antagonists. Overall, our data provide evidence that exocytosis, viewed through the autocrine inhibition of non-L-type channels, is detectable in membrane patches of approximately 1 microm2 distributed over 30%-40% of the total cell surface, while Ca2+ channels and autoreceptors are uniformly distributed over most of the cell membrane.
在牛嗜铬细胞中,参与胞吐作用的Ca2+通道会被ATP和阿片类物质有效抑制,这些物质在细胞活动期间与儿茶酚胺共同释放。这种自分泌环路导致Ca2+通道激活延迟,而先前的去极化可迅速消除这种延迟。因此,分泌产物对Ca2+通道门控的改变使得将Ca2+通道活性与分泌事件相关联成为可能。在这里,我们使用细胞贴附式膜片钳记录发现,延迟的Ca2+通道开放与局部或全细胞Ba2+刺激诱导的神经递质分泌之间存在显著相关性。该作用对N型和P/Q型通道具有特异性,并且在很大程度上可被百日咳毒素以及嘌呤能和阿片受体拮抗剂的混合物所阻断。总体而言,我们的数据表明,通过非L型通道的自分泌抑制来观察胞吐作用,在分布于细胞总表面积30%-40%的约1平方微米的膜片中是可检测到的,而Ca2+通道和自受体则均匀分布于细胞膜的大部分区域。