Albuquerque C, Oliveira S M, Coutinho-Silva R, Oliveira-Castro G M, Persechini P M
Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil.
Am J Physiol. 1993 Dec;265(6 Pt 1):C1663-73. doi: 10.1152/ajpcell.1993.265.6.C1663.
We have investigated the currents induced by extracellular ATP (ATPo), extra-cellular UTP, and other related compounds in macrophages. At potentials of -20 to -60 mV, a typical response to ATPo puffs consists of a fast-activating inward current followed by a transient outward current. The phenomenon lasts 5-20 s, but for sustained exposure to ATP the inward current persists for up to 10 min (our longest recording time). Both currents are inhibited by Mg2+, suggesting that the phenomenon is mediated by ATP4-. The outward current can be ascribed to a Ca(2+)-dependent K+ conductance, and release of Ca2+ from intracellular stores is at least in part responsible for this current. The inward current has a reversal potential of approximately 0 mV, and it is nonspecific for monovalent cations. UTP, a nucleotide that induces an increase in the cytoplasmic concentration of free Ca2+ but does not permeabilize macrophages, and ATP-gamma-S can also induce inward and outward current similar to those described for ATP, but higher doses are required. Adenosine and AMP produce no detectable effect, whereas ADP induces a small outward current. The implications of these results to the phenomenon of ATPo-induced permeabilization of macrophage membranes to large molecules are discussed.
我们研究了细胞外ATP(ATPo)、细胞外UTP及其他相关化合物在巨噬细胞中诱导产生的电流。在-20至-60 mV的电位下,对ATPo微量注射的典型反应包括一个快速激活的内向电流,随后是一个短暂的外向电流。该现象持续5 - 20秒,但对于持续暴露于ATP的情况,内向电流可持续长达10分钟(我们最长的记录时间)。两种电流均受Mg2+抑制,表明该现象由ATP4-介导。外向电流可归因于Ca(2+)依赖性K+电导,细胞内钙库释放Ca2+至少部分地导致了该电流。内向电流的反转电位约为0 mV,且对单价阳离子无特异性。UTP是一种能诱导细胞质中游离Ca2+浓度升高但不会使巨噬细胞通透的核苷酸,ATP-γ-S也能诱导出与ATP类似的内向和外向电流,但需要更高剂量。腺苷和AMP未产生可检测到的效应,而ADP诱导出一个小的外向电流。本文讨论了这些结果对ATPo诱导巨噬细胞膜对大分子通透现象的意义。