Calmels T P, Faivre J F, Cheval B, Javré J L, Rouanet S, Bril A
Department of Cardiovascular Pharmacology, SmithKline Beecham Laboratories Pharmaceutiques, 4 Rue du Chesnay Beauregard, 35760 Saint-Grégoire, France.
Biochem Biophys Res Commun. 2001 Feb 23;281(2):452-60. doi: 10.1006/bbrc.2001.4396.
Relative expression pattern of short and long isoforms of hKv4.3 channels was evaluated by RT-PCR and RPA. Electrophysiological studies were performed in HEK293 cells transfected with short or long hKv4.3 cDNA. The long variant L-hKv4.3 was the only form present in lung, pancreas, and small intestine. The short variant S-hKv4.3 was predominant in brain whereas expression levels of the two isoforms were similar in cardiac and skeletal muscles. Properties of the ionic channels encoded by L-hKv4.3 and S-hKv4.3 cDNAs were essentially similar. Cadmium chloride and verapamil inhibited hKv4.3 current (with EC50s of 0.110 +/- 0.004 mM and 492.9 +/- 15.1 microM, respectively). Verapamil also accelerated current inactivation. Another calcium channel antagonist nicardipine was found inactive. In conclusion, this study confirms that both isoforms underlie the transient outward potassium current. Moreover, calcium channel inhibitors markedly affect hKv4.3 current, an effect which must be considered when evaluating transient outward potassium channel properties in native tissues.
通过逆转录聚合酶链反应（RT-PCR）和核糖核酸酶保护分析（RPA）评估了hKv4.3通道短异构体和长异构体的相对表达模式。对转染了短或长hKv4.3 cDNA的人胚肾293（HEK293）细胞进行了电生理研究。长变体L-hKv4.3是肺、胰腺和小肠中存在的唯一形式。短变体S-hKv4.3在脑中占主导地位，而这两种异构体在心肌和骨骼肌中的表达水平相似。由L-hKv4.3和S-hKv4.3 cDNA编码的离子通道特性基本相似。氯化镉和维拉帕米抑制hKv4.3电流（其半数有效浓度[EC50]分别为0.110±0.004 mM和492.9±15.1 μM）。维拉帕米还加速了电流失活。发现另一种钙通道拮抗剂尼卡地平无活性。总之，本研究证实这两种异构体均构成瞬时外向钾电流的基础。此外，钙通道抑制剂显著影响hKv4.3电流，在评估天然组织中瞬时外向钾通道特性时必须考虑这一效应。
