Oosawa Y, Ashcroft S J, Ashcroft F M
University Laboratory of Physiology, University of Oxford, UK.
Diabetologia. 1992 Jul;35(7):619-23. doi: 10.1007/BF00400252.
This study evaluates the use of the planar lipid bilayer as a functional assay of Ca(2+)-activated K+ channel activity for use in purification of the channel protein. Ca(2+)-activated K+ channels from the plasma membrane of an insulin-secreting hamster Beta-cell line (HIT T15) were incorporated into planar lipid bilayers. The single channel conductance was 233 picoSiemens (pS) in symmetrical 140 mmol/l KCl and the channel was strongly K(+)-selective (PCl/PK = 0.046; PNa/PK = 0.027). Channels incorporated into the bilayer with two orientations. In 65% of cases, the probability of the channel being open was increased by raising calcium on the cis side of the bilayer (to which the membrane vesicles were added) or by making the cis side potential more positive. At a membrane potential of + 20 mV, which is close to the peak of the Beta-cell action potential, channel activity was half-maximal at a Ca2+ concentration of about 15 mumol/l. Charybdotoxin greatly reduced the probability of the channel being open when added to the side opposite to that at which Ca2+ activated the channel. These results resemble those found for Ca(2+)-activated K+ channels in native Beta cell membranes and indicate that the channel properties are not significantly altered by incorporation in a planar lipid bilayer.
本研究评估了平面脂质双层作为用于通道蛋白纯化的Ca(2+)激活的K+通道活性功能测定方法的用途。将来自胰岛素分泌仓鼠β细胞系(HIT T15)质膜的Ca(2+)激活的K+通道整合到平面脂质双层中。在对称的140 mmol/l KCl中,单通道电导为233皮西门子(pS),且该通道具有很强的K+选择性(PCl/PK = 0.046;PNa/PK = 0.027)。通道以两种方向整合到双层中。在65%的情况下,通过提高双层顺式侧(添加膜囊泡的一侧)的钙浓度或使顺式侧电位更正,通道开放的概率会增加。在+20 mV的膜电位下,这接近β细胞动作电位的峰值,当Ca2+浓度约为15 μmol/l时,通道活性达到最大值的一半。当向与Ca2+激活通道的一侧相对的一侧添加蝎毒素时,蝎毒素会大大降低通道开放的概率。这些结果与在天然β细胞膜中发现的Ca(2+)激活的K+通道的结果相似,表明通道特性不会因整合到平面脂质双层中而发生显著改变。