Findlay I
Laboratoire de Physiologie Comparée (UA CNRS 1121), Université de Paris XI, Orsay, France.
J Membr Biol. 1988;101(1):83-92. doi: 10.1007/BF01872823.
The effects of ADP upon the gating of ATP-sensitive K+ channels from rat ventricular myocytes have been investigated by patch-clamp single-channel current recording experiments. ADP was applied to the internal surface of excised inside-out membrane patches and depending upon the experimental protocol and the concentration it was found that ADP could either inhibit or stimulate openings of ATP-sensitive K+ channels. In the absence of inactivation, ATP-sensitive K+ channels were inhibited by ADP in a dose-dependent manner. Partially inactivated channels, on the other hand, were stimulated by low (10 to 250 microM) and inhibited by high (greater than 250 microM) concentrations of ADP. ATP-sensitive K+ channels which were being inhibited by ATP (less than 1 mM) could be opened by the simultaneous application of ADP (50 microM to 1 mM). ADP had no effect upon channels inhibited by mM concentrations of ATP. The situation was further complicated when it was found that inhibition evoked by ADP was strongly attenuated by the presence of Mg2+ ions whilst channel stimulation, whether of partially inactivated channels or channels inhibited by ATP, required the presence of Mg2+ ions. The analog of ADP, ADP beta S, always evoked inhibition of ATP-sensitive K+ channels which was not affected by the presence or absence of Mg2+ ions.
通过膜片钳单通道电流记录实验，研究了ADP对大鼠心室肌细胞ATP敏感性钾通道门控的影响。将ADP施加于切除的内面向外膜片的内表面，根据实验方案和浓度发现，ADP既可以抑制也可以刺激ATP敏感性钾通道的开放。在无失活的情况下，ADP以剂量依赖性方式抑制ATP敏感性钾通道。另一方面，部分失活的通道受到低浓度（10至250微摩尔）ADP的刺激，而受到高浓度（大于250微摩尔）ADP的抑制。被ATP（小于1毫摩尔）抑制的ATP敏感性钾通道可通过同时施加ADP（50微摩尔至1毫摩尔）而开放。ADP对被毫摩尔浓度ATP抑制的通道没有影响。当发现ADP引起的抑制作用在Mg2+离子存在时强烈减弱，而通道刺激，无论是部分失活的通道还是被ATP抑制的通道，都需要Mg2+离子存在时，情况变得更加复杂。ADP的类似物ADPβS总是引起ATP敏感性钾通道的抑制，且不受Mg2+离子存在与否的影响。
