Chan Shyue-An, Polo-Parada Luis, Smith Corey
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH 44106, USA.
Arch Biochem Biophys. 2005 Mar 1;435(1):65-73. doi: 10.1016/j.abb.2004.12.005.
Chromaffin cells of the adrenal medulla receive cholinergic input from the splanchnic nerve. Upon sympathetic activity, chromaffin cells fire action potentials that open voltage-gated calcium channels and evoke the exocytic release of catecholamines. Catecholamines then regulate homeostatic processes such as cardiac output and vascular tone. Thus control of the Ca(2+) influx in chromaffin cells represents a target for the regulation of multiple physiological functions. Previous reports utilized square pulse depolarizations to quantify the proportional exocytic response as a function of Ca(2+) channel subtype. In this study, we use perforated patch voltage clamp and action potential waveforms to depolarize cells in situ. We analyze Ca(2+) current components under conditions that match the dynamic native cell behavior. This approach revealed a greater role for P/Q-type calcium channels in evoked exocytosis than previously reported. Thus, the P/Q-type channels represent a more important control point for the regulation of catecholamine-dependent processes than previously believed.
肾上腺髓质的嗜铬细胞接受来自内脏神经的胆碱能输入。在交感神经活动时,嗜铬细胞产生动作电位,打开电压门控钙通道,引发儿茶酚胺的胞吐释放。儿茶酚胺随后调节诸如心输出量和血管张力等稳态过程。因此,控制嗜铬细胞中的Ca(2+)内流是调节多种生理功能的一个靶点。先前的报告利用方波去极化来量化作为Ca(2+)通道亚型函数的比例性胞吐反应。在本研究中,我们使用穿孔膜片钳和动作电位波形对原位细胞进行去极化。我们在与动态天然细胞行为相匹配的条件下分析Ca(2+)电流成分。这种方法揭示了P/Q型钙通道在诱发胞吐作用中比先前报道的发挥更大的作用。因此,P/Q型通道代表了一个比先前认为的更重要的调节儿茶酚胺依赖性过程的控制点。