Yu Chih-Chieh, Ai Tomohiko, Weiss James N, Chen Peng-Sheng
Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States of America; Department of Integrated Diagnostic & Therapeutics, National Taiwan University, Taipei, Taiwan.
Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States of America; Department of Molecular Pathogenesis, Division of Pathophysiology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
PLoS One. 2014 May 5;9(5):e96691. doi: 10.1371/journal.pone.0096691. eCollection 2014.
Apamin is commonly used as a small-conductance Ca2+-activated K+ (SK) current inhibitor. However, the specificity of apamin in cardiac tissues remains unclear.
To test the hypothesis that apamin does not inhibit any major cardiac ion currents.
We studied human embryonic kidney (HEK) 293 cells that expressed human voltage-gated Na+, K+ and Ca2+ currents and isolated rabbit ventricular myocytes. Whole-cell patch clamp techniques were used to determine ionic current densities before and after apamin administration.
Ca2+ currents (CACNA1c+CACNB2b) were not affected by apamin (500 nM) (data are presented as median [25th percentile;75th percentile] (from -16 [-20;-10] to -17 [-19;-13] pA/pF, P = NS), but were reduced by nifedipine to -1.6 [-3.2;-1.3] pA/pF (p = 0.008). Na+ currents (SCN5A) were not affected by apamin (from -261 [-282;-145] to -268 [-379;-132] pA/pF, P = NS), but were reduced by flecainide to -57 [-70;-47] pA/pF (p = 0.018). None of the major K+ currents (IKs, IKr, IK1 and Ito) were inhibited by 500 nM of apamin (KCNQ1+KCNE1, from 28 [20]; [37] to 23 [18]; [32] pA/pF; KCNH2+KCNE2, from 28 [24]; [30] to 27 [24]; [29] pA/pF; KCNJ2, from -46 [-48;-40] to -46 [-51;-35] pA/pF; KCND3, from 608 [505;748] to 606 [454;684]). Apamin did not inhibit the INa or ICaL in isolated rabbit ventricular myocytes (INa, from -67 [-75;-59] to -68 [-71;-59] pA/pF; ICaL, from -16 [-17;-14] to -14 [-15;-13] pA/pF, P = NS for both).
Apamin does not inhibit human cardiac Na+ currents, L-type Ca2+ currents or other major K+ currents. These findings indicate that apamin is a specific SK current inhibitor in hearts as well as in other organs.
蜂毒明肽通常用作小电导钙激活钾（SK）电流抑制剂。然而，蜂毒明肽在心脏组织中的特异性仍不清楚。
验证蜂毒明肽不抑制任何主要心脏离子电流这一假说。
我们研究了表达人电压门控钠、钾和钙电流的人胚肾（HEK）293细胞以及分离的兔心室肌细胞。采用全细胞膜片钳技术测定给予蜂毒明肽前后的离子电流密度。
钙电流（CACNA1c + CACNB2b）不受蜂毒明肽（500 nM）影响（数据表示为中位数[第25百分位数；第75百分位数]（从-16 [-20；-10]至-17 [-19；-13] pA/pF，P = 无显著性差异），但硝苯地平使其降低至-1.6 [-3.2；-1.3] pA/pF（p = 0.008）。钠电流（SCN5A）不受蜂毒明肽影响（从-261 [-282；-145]至-268 [-379；-132] pA/pF，P = 无显著性差异），但氟卡尼使其降低至-57 [-70；-47] pA/pF（p = 0.018）。500 nM蜂毒明肽不抑制任何主要钾电流（IKs、IKr、IK1和Ito）（KCNQ1 + KCNE1，从28 [20]；[37]至23 [18]；[32] pA/pF；KCNH2 + KCNE2，从28 [24]；[30]至27 [24]；[29] pA/pF；KCNJ2，从-46 [-48；-40]至-46 [-51；-35] pA/pF；KCND3，从608 [505；748]至606 [454；684]）。蜂毒明肽不抑制分离的兔心室肌细胞中的INa或ICaL（INa，从-67 [-75；-59]至-68 [-71；-59] pA/pF；ICaL，从-16 [-17；-14]至-14 [-15；-13] pA/pF，两者P均为无显著性差异）。
蜂毒明肽不抑制人心脏钠电流、L型钙电流或其他主要钾电流。这些发现表明蜂毒明肽在心脏以及其他器官中是一种特异性SK电流抑制剂。
