Ahmed Musaab, Almilaji Ahmad, Munoz Carlos, Elvira Bernat, Shumilina Ekaterina, Bock C-Thomas, Kandolf Reinhard, Lang Florian
Department of Physiology, University of Tübingen, Germany.
Department of Molecular Pathology, University of Tübingen, Germany.
Biochem Biophys Res Commun. 2014 Aug 8;450(4):1396-401. doi: 10.1016/j.bbrc.2014.07.003. Epub 2014 Jul 7.
Parvovirus B19 (B19V) can cause inflammatory cardiomyopathy and endothelial dysfunction. Pathophysiological mechanisms involved include lysophosphatidylcholine producing phospholipase A2 (PLA2) activity of the B19V capsid protein VP1. Most recently, VP1 and lysophosphatidylcholine have been shown to inhibit Na(+)/K(+) ATPase. The present study explored whether VP1 modifies the activity of Kv1.3 and Kv1.5 K(+) channels. cRNA encoding Kv1.3 or Kv1.5 was injected into Xenopus oocytes without or with cRNA encoding VP1 isolated from a patient suffering from fatal B19V-induced myocarditis. K(+) channel activity was determined by dual electrode voltage clamp. Injection of cRNA encoding Kv1.3 or Kv1.5 into Xenopus oocytes was followed by appearance of Kv K(+) channel activity, which was significantly decreased by additional injection of cRNA encoding VP1, but not by additional injection of cRNA encoding PLA2-negative VP1 mutant (H153A). The effect of VP1 on Kv current was not significantly modified by transcription inhibitor actinomycin (10 μM for 36 h) but was mimicked by lysophosphatidylcholine (1 μg/ml). The B19V capsid protein VP1 inhibits host cell Kv channels, an effect at least partially due to phospholipase A2 (PLA) dependent formation of lysophosphatidylcholine.
细小病毒B19（B19V）可导致炎症性心肌病和内皮功能障碍。涉及的病理生理机制包括B19V衣壳蛋白VP1产生溶血磷脂酰胆碱的磷脂酶A2（PLA2）活性。最近，已证明VP1和溶血磷脂酰胆碱可抑制Na(+)/K(+) ATP酶。本研究探讨了VP1是否会改变Kv1.3和Kv1.5钾通道的活性。将编码Kv1.3或Kv1.5的cRNA注射到非洲爪蟾卵母细胞中，注射时或不注射从一名因致命B19V诱导的心肌炎患者分离出的编码VP1的cRNA。通过双电极电压钳测定钾通道活性。将编码Kv1.3或Kv1.5的cRNA注射到非洲爪蟾卵母细胞后，出现了Kv钾通道活性，额外注射编码VP1的cRNA可使其显著降低，但额外注射编码PLA2阴性VP1突变体（H153A）的cRNA则不会。转录抑制剂放线菌素（10 μM，作用36小时）对VP1对Kv电流的影响无显著改变，但溶血磷脂酰胆碱（1 μg/ml）可模拟该影响。B19V衣壳蛋白VP1可抑制宿主细胞的Kv通道，这种作用至少部分归因于磷脂酶A2（PLA）依赖性溶血磷脂酰胆碱的形成。
