Pfründer D, Anghelescu I, Kreye V A
II. Physiologisches Institut, Universität Heidelberg, Germany.
Pflugers Arch. 1993 Apr;423(1-2):149-51. doi: 10.1007/BF00374972.
Vasodilatation following tissue ischemia is assumed to partially result from activation of ATP-dependent K+ channels (KATP). To assess the effect of cytosolic adenosine nucleotides, the balance of which depends on tissue pO2, on KATP, we have measured steady state outward currents (SSC) by the whole-cell clamp technique in smooth muscle cells of the guinea pig portal vein at different concentrations of ATP and ADP in the pipette solution. Glibenclamide, a selective inhibitor of KATP, was used as a pharmacological tool. With no nucleotides in the pipette solution (Ca(2+)-free), the SSC determined at +20 mV was unaffected by glibenclamide, while with 0.1 mM ATP or with 0.1 mM ADP, the SSC exhibited a glibenclamide-sensitive component indicating activation of KATP. At 5 mM ATP and no ADP, hardly any effect of glibenclamide on the SSC was detected, suggesting inhibition of KATP by this high concentration of ATP. With 0.1 mM ADP at 5 mM ATP however, activation of KATP was achieved. At 10(-7) M Ca2+ in the pipette solution, an increased SSC was measured, but the responses to the nucleotides and/or glibenclamide were not modified. These findings suggest that in vivo, ADP may be involved in the regulation of vascular KATP, linking tissue pO2 with vascular tone and tissue perfusion.
组织缺血后的血管舒张被认为部分是由ATP依赖性钾通道（KATP）的激活引起的。为了评估细胞溶质腺苷核苷酸（其平衡取决于组织pO2）对KATP的影响，我们通过全细胞膜片钳技术，在不同浓度的ATP和ADP存在于移液管溶液中的情况下，测量了豚鼠门静脉平滑肌细胞的稳态外向电流（SSC）。格列本脲是一种KATP的选择性抑制剂，用作药理学工具。当移液管溶液中没有核苷酸（无钙）时，在+20 mV下测定的SSC不受格列本脲的影响，而当有0.1 mM ATP或0.1 mM ADP时，SSC表现出格列本脲敏感成分，表明KATP被激活。在5 mM ATP且无ADP的情况下，几乎未检测到格列本脲对SSC有任何影响，表明这种高浓度的ATP抑制了KATP。然而，在5 mM ATP存在0.1 mM ADP时，KATP被激活。当移液管溶液中的Ca2+浓度为10^(-7) M时，测量到SSC增加，但对核苷酸和/或格列本脲的反应未改变。这些发现表明，在体内，ADP可能参与血管KATP的调节，将组织pO2与血管张力和组织灌注联系起来。
