Borg John J, Hancox Jules C, Spencer C Ian, Kozlowski Roland Z
Department of Pharmacology, University of Bristol, Bristol, BS8 1TD, United Kingdom.
Biochem Biophys Res Commun. 2002 Mar 22;292(1):208-15. doi: 10.1006/bbrc.2002.6631.
This report describes for the first time a novel anionic background current (I(AB)) identified in guinea-pig isolated ventricular myocytes. It also shows that I(AB) has both novel and differential pharmacology from other (cardiac) chloride currents. Using the whole-cell patch-clamp technique and external anion substitution, I(AB) was found to be outwardly rectifying and highly permeable to NO(-)(3), with a relative permeability sequence of NO(-)(3) > I(-) > Cl(-). I(AB) was not blocked by 50 microM DIDS, by hypertonic external solution, or by the nonselective protein kinase inhibitor H7-DHC. Exposure to the pyrethroid agent tefluthrin (10 microM) increased the current density of I(AB) significantly at positive voltages (P < 0.05), but had no significant effect on other cardiac chloride currents. We conclude that I(AB) possesses a distinct pharmacology and does not fall into the three major classes of cardiac chloride conductance commonly reported.
本报告首次描述了在豚鼠离体心室肌细胞中鉴定出的一种新型阴离子背景电流(I(AB))。研究还表明,I(AB)与其他(心脏)氯离子电流相比,具有独特的药理学特性。采用全细胞膜片钳技术和外部阴离子置换法,发现I(AB)呈外向整流,对NO(-)(3)具有高度通透性,相对通透性顺序为NO(-)(3) > I(-) > Cl(-)。I(AB)不受50 microM DIDS、高渗外部溶液或非选择性蛋白激酶抑制剂H7-DHC的阻断。暴露于拟除虫菊酯类药物氟氯氰菊酯(10 microM)可使I(AB)在正电压下的电流密度显著增加(P < 0.05),但对其他心脏氯离子电流无显著影响。我们得出结论,I(AB)具有独特的药理学特性,不属于通常报道的三种主要心脏氯离子电导类型。