ADRENAL CHROMAFFIN CELL NA+ CHANNELS

这些研究的目的是研究肾上腺染色质细胞神经分泌的分子基础，特别强调电压敏感的Na+通道所起的作用。本课题的具体目的包括：利用分子克隆技术测定肾上腺染色质细胞Na+通道的分子结构，在爪蟾卵母细胞和哺乳动物细胞中表达Na+通道，评估其生理和药理特性；利用反义mRNA技术消融原代培养的肾上腺染色质细胞中选定的Na+通道基因，以确定儿茶酚胺神经分泌的哪些方面是由特定的Na+通道亚基贡献的。我推测，由于其他组织中的Na+通道受到辅助β亚基的功能调节，肾上腺染色质细胞中的Na+通道β亚基将调节神经内分泌Na+通道，从而对神经分泌的调节做出重要贡献。

The goal of these proposed studies is to investigate the molecular basis of neurosecretion in adrenal chromaffin cells, with particular emphasis on the role played by voltage-sensitive Na+ channels. The specific aims of this proposal include determination of the molecular structure of adrenal chromaffin cell Na+ channels by molecular cloning techniques, expression of those Na+ channels in Xenopus oocytes and mammalian cells to assess their physiological and pharmacological properties, and finally, ablation of selected Na+ channel genes in adrenal chromaffin cells in primary culture using antisense mRNA technology to determine which aspects of catecholamine neurosecretion are contributed by specific Na+ channel subunits. I hypothesize that because Na+ channels in other tissues are functionally modulated by auxiliary beta subunits, Na+ channel beta subunits in adrenal chromaffin cells will modulate neuroendocrine Na+ channels and therefore make a significant contribution to the regulation of neurosecretion.