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非洲爪蟾胚胎培养的肌节肌细胞中ATP敏感性钾通道的生物物理、药理学及发育特性

Biophysical, pharmacological and developmental properties of ATP-sensitive K+ channels in cultured myotomal muscle cells from Xenopus embryos.

作者信息

Honoré E, Lazdunski M

机构信息

Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France.

出版信息

Pflugers Arch. 1995 Mar;429(5):607-16. doi: 10.1007/BF00373981.

Abstract

Unlike mammalian muscle cells in culture, cultured myotomal muscle cells of Xenopus embryos express ATP-sensitive K+ (KATP) channels. The KATP channels are blocked by internal ATP (half-maximal inhibition K0.5 = 16 microM) and to a lesser extent by internal ADP, are voltage independent, have an inward rectification at positive potentials and are inhibited by glibenclamide (K0.5 = 2 microM). Surprisingly, these KATP channels are not sensitive to K+ channel openers such as cromakalim. Opening of these KATP channels does not occur under normal physiological conditions. It is elicited by metabolic exhaustion of the muscle cell and it precedes the development of an irreversible rigor state. Neither intracellular acidosis nor an increase of intracellular Ca2+ are involved in KATP channel opening. Different types of K+ channels are successively expressed after plating of myotomal muscle cells: (1) sustained delayed-rectifier K+ channels; (2) KATP channels; (3) inward-rectifier K+ channels; (4) transient delayed-rectifier K+ channels. The current density associated with KATP channels far exceeds that of voltage-dependent K+ channels. Innervation controls the expression of these KATP channels. Co-culture of muscle cells with neurons from the neural tube decreases the number of active KATP channels per patch. Similarly, in situ innervated submaxillaris muscle of tadpoles at stage 50-55 has a very low density of KATP channels.

摘要

与培养的哺乳动物肌肉细胞不同,非洲爪蟾胚胎的培养肌节肌细胞表达ATP敏感性钾(KATP)通道。KATP通道被细胞内ATP阻断(半数最大抑制浓度K0.5 = 16微摩尔),且在较小程度上被细胞内ADP阻断,不依赖电压,在正电位时具有内向整流性,并被格列本脲抑制(K0.5 = 2微摩尔)。令人惊讶的是,这些KATP通道对诸如克罗卡林等钾通道开放剂不敏感。在正常生理条件下,这些KATP通道不会开放。它是由肌肉细胞的代谢耗竭引发的,且发生在不可逆的强直状态发展之前。细胞内酸中毒和细胞内Ca2+的增加均不参与KATP通道的开放。肌节肌细胞接种后会相继表达不同类型的钾通道:(1)持续延迟整流钾通道;(2)KATP通道;(3)内向整流钾通道;(4)瞬时延迟整流钾通道。与电压依赖性钾通道相比,与KATP通道相关的电流密度要高得多。神经支配控制这些KATP通道的表达。肌肉细胞与神经管神经元共培养会减少每个膜片上活性KATP通道的数量。同样,在50 - 55期蝌蚪原位受神经支配的颌下肌中,KATP通道的密度非常低。

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