Verkerk A O, Tan H L, Ravesloot J H
Department of Physiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Acta Physiol Scand. 2004 Mar;180(3):239-47. doi: 10.1111/j.0001-6772.2003.01252.x.
Various cationic membrane channels contribute to the heterogeneity of action potential configuration between the transmural layers of the left ventricle. The role of anionic membrane channels is less intensively studied. We investigated the role of the Ca2+-activated Cl- current, ICl(Ca), in transmural electrical heterogeneity.
We determined the density of ICl(Ca) and its physiological role in subepicardial and subendocardial ventricular myocytes of rabbit using the patch-clamp technique. ICl(Ca) was measured as the 4,4'diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) sensitive current. The current-voltage relationships and the densities of ICl(Ca) were similar in subepicardial and subendocardial myocytes. However, the functional role of ICl(Ca) exhibited striking differences. In subendocardial myocytes, blockade of ICl(Ca) by DIDS increased action potential duration (APD) significantly at all measured stimulus frequencies (3.33-0.2 Hz). In subepicardial myocytes, ICl(Ca) blockade increased APD only at 3.33 Hz, but not at the lower stimulus frequencies. At 1 Hz, ICl(Ca) blockade in subepicardial myocytes only caused an APD increase when the transient outward K+ current, Ito1, was blocked.
The densities and gating properties of ICl(Ca) are similar in subepicardial and subendocardial myocytes. ICl(Ca) contributes to APD shortening in subendocardial, but not in subepicardial myocytes except at 3.33 Hz. These differences in functional expression of ICl(Ca) reduce the electrical heterogeneity in rabbit left ventricle.
多种阳离子膜通道导致左心室跨壁各层动作电位形态的异质性。阴离子膜通道的作用研究较少。我们研究了钙激活氯电流（ICl(Ca)）在跨壁电异质性中的作用。
我们采用膜片钳技术测定了兔心外膜下和心内膜下心室肌细胞中ICl(Ca)的密度及其生理作用。ICl(Ca)被测量为对4,4'-二异硫氰基芪-2,2'-二磺酸（DIDS）敏感的电流。心外膜下和心内膜下心肌细胞中ICl(Ca)的电流-电压关系和密度相似。然而，ICl(Ca)的功能作用表现出显著差异。在心内膜下心肌细胞中，DIDS阻断ICl(Ca)在所有测量的刺激频率（3.33 - 0.2 Hz）下均显著增加动作电位时程（APD）。在心外膜下心肌细胞中，ICl(Ca)阻断仅在3.33 Hz时增加APD，而在较低刺激频率下则无此作用。在1 Hz时，心外膜下心肌细胞中ICl(Ca)的阻断仅在瞬时外向钾电流（Ito1）被阻断时才导致APD增加。
心外膜下和心内膜下心肌细胞中ICl(Ca)的密度和门控特性相似。ICl(Ca)有助于心内膜下心肌细胞的APD缩短，但在心外膜下心肌细胞中除3.33 Hz外则无此作用。ICl(Ca)功能表达的这些差异减少了兔左心室的电异质性。
