Cav1.3 channels produce persistent calcium sparklets, but Cav1.2 channels are responsible for sparklets in mouse arterial smooth muscle
Cav1.3 channels produce persistent calcium sparklets, but Cav1.2 channels are responsible for sparklets in mouse arterial smooth muscle
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DOI：
10.1152/ajpheart.00450.2007
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发表时间：
2007-09-01
影响因子：
4.8
通讯作者：
Santana, Luis F.
中科院分区：
文献类型：
--
作者：
Navedo, Manuel F.;Amberg, Gregory C.;Santana, Luis F.
钙离子通道是由L型钙离子通道的单个或簇开放引起的细胞内钙离子局部升高。在动脉肌细胞中，钙(+)火花调节局部和整体细胞内钙(+)。目前，这些细胞内的L型钙离子通道的分子同一性尚不清楚。在此，我们验证了电压门控钙通道-α1.3亚单位(Ca(V)1.3)可以产生小鼠动脉肌细胞内钙(+)小枝的假设，以及小鼠动脉肌细胞中钙(V)1.2和/或钙(V)1.3通道负责小鼠动脉肌细胞内小钙(+)小枝的假设。首先，我们研究了tsA201细胞中单个Ca(V)1.3通道的功能特性。以110 mM Ba2(+)为载流子，Ca(V)1.3通道的电导为20ps。此值与Ca(V)1.2和天然L型钙离子通道相似。如前面针对Ca(V)1.2通道所示，Cav1.3通道可以在两种门控模式下运行，其特征是打开时间短和长。表达的Ca(V)1.3通道也产生了钙离子小火花。Ca(V)1.3小片具有与Ca(V)1.2和天然L类通道相似的特性，包括量子幅度、二氢吡啶敏感性、双峰门控和双事件持续时间。然而，动脉肌细胞电导和钙电流(ICa)稳态失活的电压依赖关系与表达Ca(V)1.2通道的细胞相似，而不是Ca(V)1.3通道。此外，硝苯地平(10mU M)可消除野生型心肌细胞中的钙离子，但不能消除表达二氢吡啶不敏感的钙离子通道的心肌细胞中的钙离子。因此，在分离的动脉肌细胞中未检测到Ca(V)1.3转录本和蛋白。我们的结论是，虽然Ca(V)1.3通道可以产生Ca(+)小颗粒，但Ca(V)1.2通道位于ICa和Ca(+)小颗粒之下，从而导致二氢吡啶敏感的Ca(+)内流进入小鼠动脉心肌细胞。
Ca2(+) sparklets are local elevations in intracellular Ca2(+) produced by the opening of a single or a cluster of L-type Ca2(+) channels. In arterial myocytes, Ca2(+) sparklets regulate local and global intracellular Ca2(+). At present, the molecular identity of the L-type Ca2(+) channels underlying Ca2(+) sparklets in these cells is undetermined. Here, we tested the hypotheses that voltage-gated calcium channel-alpha 1.3 subunit (Ca(v)1.3) can produce Ca2(+) sparklets and that Ca(v)1.2 and/or Ca(v)1.3 channels are responsible for Ca2(+) sparklets in mouse arterial myocytes. First, we investigated the functional properties of single Ca(v)1.3 channels in tsA201 cells. With 110 mM Ba2(+) as the charge carrier, Ca(v)1.3 channels had a conductance of 20 pS. This value is similar to that of Ca(v)1.2 and native L-type Ca2(+) channels. As previously shown for Ca(v)1.2 channels, Cav1.3 channels can operate in two gating modes characterized by short and long open times. Expressed Ca(v)1.3 channels also produced Ca2(+) sparklets. Ca(v)1.3 sparklets had properties similar to those produced by Ca(v)1.2 and native L-type channels, including quantal amplitude, dihydropyridine sensitivity, bimodal gating, and dual-event duration times. However, the voltage dependencies of conductance and steady-state inactivation of the Ca2(+) current (ICa) in arterial myocytes were similar to those recorded from cells expressing Ca(v)1.2 but not Ca(v)1.3 channels. Furthermore, nifedipine (10 mu M) eliminated Ca2(+) sparklets in wild-type myocytes but not in myocytes expressing dihydropyridine-insensitive Ca(v)1.2 channels. Accordingly, Ca(v)1.3 transcript and protein were not detected in isolated arterial myocytes. We conclude that although Ca(v)1.3 channels can produce Ca2(+) sparklets, Ca(v)1.2 channels underlie ICa, Ca2(+) sparklets, and hence dihydropyridine-sensitive Ca2(+) influx in mouse arterial myocytes.