Brink P R, Cronin K, Banach K, Peterson E, Westphale E M, Seul K H, Ramanan S V, Beyer E C
Department of Physiology and Biophysics, State University of New York at Stony Brook, 11974, USA.
Am J Physiol. 1997 Oct;273(4):C1386-96. doi: 10.1152/ajpcell.1997.273.4.C1386.
Homomeric gap junction channels are composed solely of one connexin type, whereas heterotypic forms contain two homomeric hemichannels but the six identical connexins of each are different from each other. A heteromeric gap junction channel is one that contains different connexins within either or both hemichannels. The existence of heteromeric forms has been suggested, and many cell types are known to coexpress connexins. To determine if coexpressed connexins would form heteromers, we cotransfected rat connexin43 (rCx43) and human connexin37 (hCx37) into a cell line normally devoid of any connexin expression and used dual whole cell patch clamp to compare the observed gap junction channel activity with that seen in cells transfected only with rCx43 or hCx37. We also cocultured cells transfected with hCx37 or rCx43, in which one population was tagged with a fluorescent marker to monitor heterotypic channel activity. The cotransfected cells possessed channel types unlike the homotypic forms of rCx43 or hCx37 or the heterotypic forms. In addition, the noninstantaneous transjunctional conductance-transjunctional voltage (Gj/Vj) relationship for cotransfected cell pairs showed a large range of variability that was unlike that of the homotypic or heterotypic form. The heterotypic cell pairs displayed asymmetric voltage dependence. The results from the heteromeric cell pairs are inconsistent with summed behavior of two independent homotypic populations or mixed populations of homotypic and heterotypic channels types. The Gj/Vj data imply that the connexin-to-connexin interactions are significantly altered in cotransfected cell pairs relative to the homotypic and heterotypic forms. Heteromeric channels are a population of channels whose characteristics could well impact differently from their homotypic counterparts with regard to multicellular coordinated responses.
同型间隙连接通道仅由一种连接蛋白类型组成，而异型形式包含两个同型半通道，但每个半通道的六个相同连接蛋白彼此不同。异源间隙连接通道是指在一个或两个半通道中包含不同连接蛋白的通道。已有研究表明存在异源形式，并且已知许多细胞类型会共同表达连接蛋白。为了确定共同表达的连接蛋白是否会形成异聚体，我们将大鼠连接蛋白43（rCx43）和人连接蛋白37（hCx37）共转染到一个通常不表达任何连接蛋白的细胞系中，并使用双全细胞膜片钳来比较观察到的间隙连接通道活性与仅转染rCx43或hCx37的细胞中的活性。我们还将转染了hCx37或rCx43的细胞进行共培养，其中一个群体用荧光标记物标记以监测异型通道活性。共转染的细胞具有不同于rCx43或hCx37的同型形式或异型形式的通道类型。此外，共转染细胞对的非瞬时跨连接电导 - 跨连接电压（Gj/Vj）关系显示出很大的变异性，这与同型或异型形式不同。异型细胞对表现出不对称的电压依赖性。异源细胞对的结果与两个独立同型群体或同型和异型通道类型的混合群体的总和行为不一致。Gj/Vj数据表明，相对于同型和异型形式，共转染细胞对中连接蛋白与连接蛋白之间的相互作用发生了显著改变。异源通道是一类通道群体，其特性在多细胞协调反应方面可能与同型对应物产生不同的影响。
