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Regional differences in the expression of tetrodotoxin-sensitive inward Ca2+ and outward Cs+/K+ currents in mouse and human ventricles.
Channels ( IF 3.3 ) Pub Date : 2019-02-01 , DOI: 10.1080/19336950.2019.1568146
Wei Wang 1 , Rebecca L Mellor 1 , Jeanne M Nerbonne 1, 2 , C William Balke 1, 2
Affiliation  

Tetrodotoxin (TTX) sensitive inward Ca2+ currents, ICa(TTX), have been identified in cardiac myocytes from several species, although it is unclear if ICa(TTX) is expressed in all cardiac cell types, and if ICa(TTX) reflects Ca2+ entry through the main, Nav1.5-encoded, cardiac Na+ (Nav) channels. To address these questions, recordings were obtained with 2 mm Ca2+ and 0 mm Na+ in the bath and 120 mm Cs+ in the pipettes from myocytes isolated from adult mouse interventricular septum (IVS), left ventricular (LV) endocardium, apex, and epicardium and from human LV endocardium and epicardium. On membrane depolarizations from a holding potential of −100 mV, ICa(TTX) was identified in mouse IVS and LV endocardial myocytes and in human LV endocardial myocytes, whereas only TTX-sensitive outward Cs+/K+ currents were observed in mouse LV apex and epicardial myocytes and human LV epicardial myocytes. The inward Ca2+, but not the outward Cs+/K+, currents were blocked by mm concentrations of MTSEA, a selective blocker of cardiac Nav1.5-encoded Na+ channels. In addition, in Nav1.5-expressing tsA-201 cells, ICa(TTX) was observed in 3 (of 20) cells, and TTX-sensitive outward Cs+/K+ currents were observed in the other (17) cells. The time- and voltage-dependent properties of the TTX-sensitive inward Ca2+ and outward Cs+/K+ currents recorded in Nav1.5-expressing tsA-201 were indistinguishable from native currents in mouse and human cardiac myocytes. Overall, the results presented here suggest marked regional, cell type-specific, differences in the relative ion selectivity, and likely the molecular architecture, of native SCN5A-/Scn5a- (Nav1.5-) encoded cardiac Na+ channels in mouse and human ventricles.



中文翻译:

河豚毒素敏感的内向Ca2 +和外向Cs + / K +电流在小鼠和人心室中表达的区域差异。

河豚毒素(TTX)敏感的内向Ca 2+电流I Ca(TTX)在几种物种的心肌细胞中均已鉴定,尽管尚不清楚I Ca(TTX)是否在所有心脏细胞类型中都表达,以及I Ca( TTX)通过主要的Nav1.5编码的心脏Na +(Nav)通道反映Ca 2+进入。为了解决这些问题,在浴中使用2 m m Ca 2+和0 m m Na +以及120 m m Cs +进行记录。从成人成年小鼠心室间隔(IVS),左心室(LV)心内膜,根尖和心外膜以及人LV心内膜和心外膜分离的心肌细胞中获得 从-100 mV的保持电位进行膜去极化时,在小鼠IVS和LV心内膜心肌细胞和人LV心内膜心肌细胞中鉴定到I Ca(TTX),而在小鼠LV中仅观察到TTX敏感的向外Cs + / K +电流心尖和心外膜心肌细胞和人LV心外膜心肌细胞。内向Ca 2+而非外向Cs + / K +电流被m浓度的MTSEA阻断,MTSEA是心脏Nav1.5编码的Na的选择性阻断剂+频道。另外,在表达Nav1.5的tsA-201细胞中,在3个(共20个)细胞中观察到了I Ca(TTX),而在其他(17个)细胞中观察到了TTX敏感的向外Cs + / K +电流。在表达Nav1.5的tsA-201中记录的TTX敏感的向内Ca 2+和向外Cs + / K +电流的时间和电压依赖性与在小鼠和人类心肌细胞中的自然电流没有区别。总体而言,此处显示的结果表明,天然SCN5A- / Scn5a-的区域特异性,细胞类型特异性,相对离子选择性差异以及可能的分子结构(Nav1.5-)编码的小鼠和人类心室中的心脏Na +通道。

更新日期:2019-02-01
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