Tang Kim San, Wang Nan, Tse Amy, Tse Frederick W
Department of Pharmacology and Centre for Neuroscience, University of Alberta, Edmonton, Alberta, Canada.
Biophys J. 2007 Apr 15;92(8):2735-46. doi: 10.1529/biophysj.106.088997. Epub 2007 Jan 19.
Using carbon fiber amperometry, we exploited the natural variation in quantal size (Q) among individual granules in rat chromaffin cells to examine the influence of Q on quantal release kinetics. Although it is generally accepted that granules with larger Q have slower kinetics of release, we found that this trend was applicable only to granules with Q(1/3) < 0.6 pC(1/3). Granules with larger Q adapted specific mechanisms to maintain a rapid kinetic of release. The semistable fusion pores in the large-Q granules persisted for a longer duration and could reach a bigger size before the onset of very rapid dilation to allow a longer and larger foot signal. Most importantly, a large proportion of large-Q granules maintained a relatively short half-width in the main spike. This suggests that the most rapid phase of fusion pore dilation in many large-Q granules may be faster than that in small-Q granules. Moreover, cAMP selectively advanced the onset of the rapid dilation of the fusion pore in the large- but not the small-Q granules. Thus, our finding raises the possibility that fusion pore and/or granule matrix in small- and large-Q granules may have different molecular structures.
利用碳纤维安培法,我们利用大鼠嗜铬细胞中单个颗粒之间量子大小(Q)的自然变化来研究Q对量子释放动力学的影响。尽管人们普遍认为具有较大Q值的颗粒释放动力学较慢,但我们发现这种趋势仅适用于Q(1/3) < 0.6 pC(1/3)的颗粒。具有较大Q值的颗粒采用了特定机制来维持快速的释放动力学。大Q颗粒中的半稳定融合孔持续时间更长,并且在开始非常快速扩张之前可以达到更大的尺寸,从而允许更长和更大的足部信号。最重要的是,很大一部分大Q颗粒在主峰中保持相对较短的半高宽。这表明许多大Q颗粒中融合孔扩张的最快速阶段可能比小Q颗粒中的更快。此外,cAMP选择性地提前了大Q颗粒而非小Q颗粒中融合孔快速扩张的起始时间。因此,我们的发现增加了小Q颗粒和大Q颗粒中的融合孔和/或颗粒基质可能具有不同分子结构的可能性。