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在非洲爪蟾卵母细胞中,钾通道开放剂作用于两种不同类型的通道。

Two different types of channels are targets for potassium channel openers in Xenopus oocytes.

作者信息

Honoré E, Lazdunski M

机构信息

Institut de Pharmacologie Moléculaire et Cellulaire du CNRS, Valbonne, France.

出版信息

FEBS Lett. 1991 Aug 5;287(1-2):75-9. doi: 10.1016/0014-5793(91)80019-y.

Abstract

K+ channel openers elicit K+ currents in follicle-enclosed Xenopus oocytes. The most potent activators are the pinacidil derivatives P1075 and P1060. The rank order of potency to activate K+ currents in follicle-enclosed oocytes was: P1075 (K0.5:5 microM) greater than P1060 (K0.5:12 microM) greater than BRL38227 (lemakalim) (K0.5:77 microM) greater than RP61410 (K0.5:100 microM) greater than (-)pinacidil (K0.5:300 microM). Minoxidil sulfate, nicorandil, RP49356 and diazoxide were ineffective. Activation by the K+ channel openers could be abolished by the antidiabetic sulfonylurea glibenclamide. It was not affected by the blocker of the Ca(2+)-activated K+ channels charybdotoxin. The various K+ channel openers failed to activate glibenclamide-sensitive K+ channels in defolliculated oocytes, but BRL derivatives (K0.5 for BRL38226 is 150 microM) and RP61419 inhibited a background current. The channel responsible for this background current is K+ permeable but not fully selective for K+. It is resistant to glibenclamide. It is inhibited by Ba2+, 4-aminopyridine, Co2+, Ni2+ and La3+.

摘要

钾通道开放剂可在卵泡包裹的非洲爪蟾卵母细胞中引发钾电流。最有效的激活剂是匹那地尔衍生物P1075和P1060。在卵泡包裹的卵母细胞中激活钾电流的效力排序为:P1075(半数激活浓度[K0.5]:5微摩尔)>P1060(K0.5:12微摩尔)>BRL38227(利马卡林)(K0.5:77微摩尔)>RP61410(K0.5:100微摩尔)>(-)匹那地尔(K0.5:300微摩尔)。硫酸米诺地尔、尼可地尔、RP49356和二氮嗪无效。钾通道开放剂的激活作用可被抗糖尿病磺脲类药物格列本脲消除。它不受钙激活钾通道阻断剂卡律蝎毒素的影响。各种钾通道开放剂未能激活去卵泡卵母细胞中格列本脲敏感的钾通道,但BRL衍生物(BRL38226的K0.5为150微摩尔)和RP61419可抑制背景电流。负责这种背景电流的通道对钾离子具有通透性,但对钾离子的选择性不完全。它对格列本脲有抗性。它可被钡离子、4-氨基吡啶、钴离子、镍离子和镧离子抑制。

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