Leuranguer V, Monteil A, Bourinet E, Dayanithi G, Nargeot J
Physiopathologie des Canaux Ioniques, Institut de Génétique Humaine-Centre National de la Recherche Scientifique (CNRS) UPR 1142, 34396 Montpellier cedex 05, France.
Am J Physiol Heart Circ Physiol. 2000 Nov;279(5):H2540-8. doi: 10.1152/ajpheart.2000.279.5.H2540.
T-type Ca(2+) channels have been suggested to play a role in cardiac automaticity, cell growth, and cardiovascular remodeling. Although three genes encoding for a T-type Ca(2+) channel have been identified, the nature of the isoform(s) supporting the cardiac T-type Ca(2+) current (I(Ca,T)) has not yet been determined. We describe the postnatal evolution of I(Ca,T) density in freshly dissociated rat atrial and ventricular myocytes and its functional properties at peak current density in young atrial myocytes. I(Ca,T) displays a classical low activation threshold, rapid inactivation kinetics, negative steady-state inactivation, slow deactivation, and the presence of a window current. Interestingly, I(Ca,T) is poorly sensitive to Ni(2+) and insensitive to R-type current toxin SNX-482. RT-PCR experiments and comparison of functional properties with recombinant Ca(2+) channel subtypes suggest that neonatal I(Ca,T) is related to the alpha(1G)-subunit. Atrial natriuretic factor (ANF) secretion was measured using peptide radioimmunoassays in atrial tissue. Pharmacological dissection of ANF secretion indicates an important contribution of I(Ca,T) to Ca(2+) signaling during the neonatal period.
T型Ca(2+)通道被认为在心脏自律性、细胞生长和心血管重塑中发挥作用。尽管已经鉴定出三个编码T型Ca(2+)通道的基因，但支持心脏T型Ca(2+)电流（I(Ca,T)）的同工型的性质尚未确定。我们描述了新鲜分离的大鼠心房和心室肌细胞中I(Ca,T)密度的出生后演变及其在年轻心房肌细胞中峰值电流密度时的功能特性。I(Ca,T)表现出典型的低激活阈值、快速失活动力学、负稳态失活、缓慢失活以及存在窗电流。有趣的是，I(Ca,T)对Ni(2+)敏感性较差，对R型电流毒素SNX-482不敏感。逆转录聚合酶链反应（RT-PCR）实验以及与重组Ca(2+)通道亚型功能特性的比较表明，新生大鼠的I(Ca,T)与α(1G)亚基相关。使用肽放射免疫测定法测量心房组织中的心房利钠因子（ANF）分泌。对ANF分泌的药理学分析表明，I(Ca,T)在新生儿期对Ca(2+)信号传导有重要贡献。
