Sitsapesan R
Cardiac Medicine, Imperial College School of Medicine, Dovehouse Street, London SW3 6LY, UK.
J Membr Biol. 1999 Mar 15;168(2):159-68. doi: 10.1007/s002329900506.
The mechanisms involved in 4,4'-diisothiocyanostilbene-2, 2'-disulfonic acid (DIDS)- and 4,4'-dibenzamidostilbene-2, 2'-disulfonic acid (DBDS)- modification of sheep cardiac ryanodine receptor (RyR) channel function have been investigated. DIDS (50-500 microm) exerts at least three effects on single channel function. With Ca2+ as the permeant ion, DIDS increases both channel open probability (Po) and single channel conductance in a similar manner to the effects observed with suramin. Both effects occur immediately and are fully reversible. Similar effects were observed with DBDS (10 microm-2 mm), a compound with the 4,4'-NCS groups of DIDS replaced with NHCOC6H5. DIDS (500 microm) also caused irreversible modification to the fully open channel level in 74% of the channels. This effect was not observed with suramin or DBDS (10 microm-1 mm). Competition studies with DBDS and suramin coupled with the close similarities in the effects of DIDS, DBDS and suramin on gating and conduction suggest that these ligands may all bind to the same sites on RyR. The DIDS-induced irreversible modification to the fully open state may result from the binding of the isothiocyanate groups to positively charged amino acids at or near the suramin binding sites although it is possible that this modification is unrelated to its other effects on channel function.
已对4,4'-二异硫氰基芪-2,2'-二磺酸（DIDS）和4,4'-二苯甲酰胺基芪-2,2'-二磺酸（DBDS）对绵羊心脏兰尼碱受体（RyR）通道功能的修饰机制进行了研究。DIDS（50 - 500微摩尔）对单通道功能至少有三种作用。以Ca2+作为通透离子时，DIDS增加通道开放概率（Po）和单通道电导，其方式与用苏拉明观察到的作用相似。这两种作用立即发生且完全可逆。用DBDS（10微摩尔 - 2毫摩尔）也观察到了类似的作用，DBDS是一种将DIDS的4,4'-NCS基团替换为NHCOC6H5的化合物。DIDS（500微摩尔）还使74%的通道在完全开放通道水平发生不可逆修饰。用苏拉明或DBDS（10微摩尔 - 1毫摩尔）未观察到这种作用。用DBDS和苏拉明进行的竞争研究，以及DIDS、DBDS和苏拉明对门控和传导作用的密切相似性表明，这些配体可能都结合到RyR上的相同位点。DIDS诱导的对完全开放状态的不可逆修饰可能是由于异硫氰酸酯基团与苏拉明结合位点处或附近带正电荷的氨基酸结合所致，尽管这种修饰有可能与其对通道功能的其他作用无关。
