Schram Gernot, Pourrier Marc, Wang Zhiguo, White Michel, Nattel Stanley
Department of Medicine and Research Center, Montreal Heart Institute, 5000 Belanger Street East, Montreal, Quebec, Canada H1T 1C8.
Cardiovasc Res. 2003 Aug 1;59(2):328-38. doi: 10.1016/s0008-6363(03)00366-3.
Kir2 subunits are believed to underlie the cardiac inwardly rectifying current I(K1). The subunit composition of native I(K1) currents is uncertain, and it has been suggested that heteromultimer formation may play a role.
We studied Ba(2+) block of homo- and heteromeric Kir2 channels in Xenopus oocytes and compared the properties observed to those of human cardiac I(K1) in cells isolated from myocardial biopsies of normal human hearts.
Homomeric expression of Kir2.1 and Kir2.3 produced currents with similar Ba(2+) sensitivities (e.g. IC(50) at -120 mV: 16.2+/-3.4, n=11 and 18.5+/-2.1, n=10, respectively), but these were less sensitive to Ba(2+) than native I(K1) (4.7+/-0.5 microM, n=10, P=0.001, P<0.001, respectively) and had different Ba(2+) blocking kinetics from cardiac I(K1). Kir2.2 sensitivity was similar to cardiac I(K1) (e.g., 2.8+/-0.4 microM, Kir2.2, n=9, vs. 4.7+/-0.5 microM for I(K1)), but the blocking kinetics of Kir2.2 were faster than those of I(K1). Currents resulting from co-expression of Kir2 subunits had similar Ba(2+) sensitivities and blocking kinetics among groups and were similar to I(K1) in both Ba(2+) sensitivity (e.g., IC(50) at -120 mV: 4.5+/-1.0, 2.5+/-0.5, and 2.3+/-0.4 microM for co-injected Kir2.1/2.2, n=6, Kir2.1/2.3, n=5, and Kir2.2/2.3, n=4, respectively) and blocking kinetics.
Co-injection of Kir2 subunits results in currents with Ba(2+) blocking properties different from homomeric Kir2 expression but similar to cardiac I(K1). These observations suggest that a substantial proportion of native I(K1) may result from heteromultimer formation among diverse Kir2 family subunits.
Kir2亚基被认为是心脏内向整流电流I(K1)的基础。天然I(K1)电流的亚基组成尚不确定，有人提出异源多聚体的形成可能起作用。
我们研究了非洲爪蟾卵母细胞中同源和异源Kir2通道的Ba(2+)阻断情况，并将观察到的特性与从正常人心肌活检分离的细胞中的人类心脏I(K1)特性进行比较。
Kir2.1和Kir2.3的同源表达产生的电流具有相似的Ba(2+)敏感性（例如，在-120 mV时的IC(50)：分别为16.2±3.4，n = 11和18.5±2.1，n = 10），但这些电流对Ba(2+)的敏感性低于天然I(K1)（分别为4.7±0.5 μM，n = 10，P = 0.001，P < 0.001），并且与心脏I(K1)具有不同的Ba(2+)阻断动力学。Kir2.2的敏感性与心脏I(K1)相似（例如，Kir2.2为2.8±0.4 μM，n = 9，而I(K1)为4.7±0.5 μM），但Kir2.2的阻断动力学比I(K1)快。Kir2亚基共表达产生的电流在各组之间具有相似的Ba(2+)敏感性和阻断动力学，并且在Ba(2+)敏感性（例如，在-120 mV时的IC(50)：共注射Kir2.1/2.2时为4.5±1.0 μM，n = 6；Kir2.1/2.3时为2.5±0.5 μM，n = 5；Kir2.2/2.3时为2.3±0.4 μM，n = 4）和阻断动力学方面均与I(K1)相似。
共注射Kir2亚基产生的电流具有与同源Kir2表达不同但与心脏I(K1)相似的Ba(2+)阻断特性。这些观察结果表明，相当一部分天然I(K1)可能是由不同的Kir2家族亚基之间形成异源多聚体导致的。
