Liu Q Y, Rasmusson R L, Liu Q X, Strauss H C
Department of Pharmacology, Medicine and Biomedical Engineering, Duke University Medical Center, Durham, North Carolina, USA.
Can J Cardiol. 1998 Feb;14(2):275-80.
The nature of open state block was characterized in isolated canine cardiac sarcoplasmic reticulum (SR) potassium channel incorporated into planar lipid bilayers. 4-Aminopyridine (4-AP) blocked the open conductance state of the potassium channels in a voltage-dependent manner. Blockade was reversible, occurred from either the cis (cytoplasmic) or the trans (lumenal) side and was competitive with potassium ions. Reversal potential measurements indicated that this channel was impermeable to 4-AP. Measured effective electrical distances were roughly symmetrical and indicated penetration of 0.39 and 0.42 of the membrane electrical field from the cis and trans sides, respectively. Effective electrical distance was insensitive to potassium ion concentration in the range 50 to 200 mM and indicated that 4-AP was able to penetrate relatively deeply into the pore compared with blockade of sarcolemmal potassium channels. Potassium ion concentration and voltage dependence of 4-AP blockade were consistent with a two binding site blockade model, similar to the model used previously to describe calcium ion blockade of the SR potassium ion channel. Unlike calcium blockade, however, 4-AP blocked from either cis or trans in a similar manner, suggesting a distinct binding site for each of these two blockers. Open channel, voltage-dependent blockade of the SR potassium channel by 4-AP is in marked contrast to its action on sarcolemmal potassium channels and suggests that either 4-AP penetrates much farther into the potassium channel permeation pathway than was previously believed, or the SR potassium channel has a very different physical pore arrangement from that of sarcolemmal potassium channels.
通过将分离的犬心脏肌浆网（SR）钾通道整合到平面脂质双分子层中，对开放状态阻断的性质进行了表征。4-氨基吡啶（4-AP）以电压依赖性方式阻断钾通道的开放电导状态。阻断是可逆的，可从顺式（细胞质）或反式（管腔）侧发生，并且与钾离子具有竞争性。反转电位测量表明该通道对4-AP不可渗透。测得的有效电距离大致对称，分别表明从顺式和反式侧穿透膜电场的0.39和0.42。有效电距离在50至200 mM范围内对钾离子浓度不敏感，表明与肌膜钾通道的阻断相比，4-AP能够相对深入地渗透到孔中。4-AP阻断的钾离子浓度和电压依赖性与双结合位点阻断模型一致，类似于先前用于描述SR钾离子通道钙离子阻断的模型。然而，与钙阻断不同，4-AP从顺式或反式侧以类似方式阻断，表明这两种阻断剂各自具有独特的结合位点。4-AP对SR钾通道的开放通道、电压依赖性阻断与其对肌膜钾通道的作用形成鲜明对比，这表明要么4-AP比以前认为的更深入地渗透到钾通道渗透途径中，要么SR钾通道的物理孔排列与肌膜钾通道有很大不同。
