The skeletal L-type Ca(2+) current is a major contributor to excitation-coupled Ca(2+) entry.
The skeletal L-type Ca(2+) current is a major contributor to excitation-coupled Ca(2+) entry.
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DOI：
10.1085/jgp.200810105
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发表时间：
2009-01
影响因子：
3.8
通讯作者：
Beam, Kurt G.
中科院分区：
文献类型：
--
作者：
Bannister, Roger A.;Pessah, Isaac N.;Beam, Kurt G.
兴奋偶联钙离子内流（ECCE）是指细胞外钙离子进入骨骼肌细胞，这是对延长的去极化或脉冲串的反应，取决于质膜中1，4-二氢吡啶受体（DHPR）和肌浆网（SR）膜中1型兰尼碱受体的存在。ECCE途径可被药物阻断，这些药物也可阻断钙池操作的Ca 2+进入，可被丹曲林抑制，对DHP拮抗剂硝苯地平（1 μM）相对不敏感，对Mn 2+具有渗透性。在这里，我们研究了这些药物对通过DHPR传导的L型Ca 2+电流的影响。我们发现，非特异性阳离子通道拮抗剂（2-APB，SKF 96356，La ~（3+）和Gd ~（3+））和丹曲林都抑制L-型Ca ~（2+）电流。此外，完全（>97%）阻断L-型电流需要硝苯地平浓度>10 μM。像ECCE一样，L型Ca 2+通道在没有外部Ca 2+的情况下显示出对Mn 2+的渗透性，并产生在长时间（约10秒）去极化期间持续存在的Ca 2+电流。该电流似乎有助于在完整肌管的长时间KCl去极化期间观察到的Ca 2+瞬变，因为（1）正常肌管中的瞬变在缺乏外部Ca 2+的情况下衰减得更快;（2）表达SkEIIIK的发育不良肌管中的瞬时（一种DHPR α 1 S孔突变体，被认为仅传导单价阳离子）在Ca 2 +-Ca 2+浓度方面与正常肌管的时间过程相似。（3）用200 μM ryanodine阻断SR Ca 2+释放后，正常肌管仍显示大量Ca 2+瞬变，而在表达SkEIIIK的发育不良肌管中未检测到瞬变。总的来说，这些结果表明骨骼肌L型通道是ECCE导致的Ca 2+进入的主要贡献者。
The term excitation-coupled Ca2+ entry (ECCE) designates the entry of extracellular Ca2+ into skeletal muscle cells, which occurs in response to prolonged depolarization or pulse trains and depends on the presence of both the 1,4-dihydropyridine receptor (DHPR) in the plasma membrane and the type 1 ryanodine receptor in the sarcoplasmic reticulum (SR) membrane. The ECCE pathway is blocked by pharmacological agents that also block store-operated Ca2+ entry, is inhibited by dantrolene, is relatively insensitive to the DHP antagonist nifedipine (1 μM), and is permeable to Mn2+. Here, we have examined the effects of these agents on the L-type Ca2+ current conducted via the DHPR. We found that the nonspecific cation channel antagonists (2-APB, SKF 96356, La3+, and Gd3+) and dantrolene all inhibited the L-type Ca2+ current. In addition, complete (>97%) block of the L-type current required concentrations of nifedipine >10 μM. Like ECCE, the L-type Ca2+ channel displays permeability to Mn2+ in the absence of external Ca2+ and produces a Ca2+ current that persists during prolonged (∼10-second) depolarization. This current appears to contribute to the Ca2+ transient observed during prolonged KCl depolarization of intact myotubes because (1) the transients in normal myotubes decayed more rapidly in the absence of external Ca2+; (2) the transients in dysgenic myotubes expressing SkEIIIK (a DHPR α1S pore mutant thought to conduct only monovalent cations) had a time course like that of normal myotubes in Ca2+-free solution and were unaffected by Ca2+ removal; and (3) after block of SR Ca2+ release by 200 μM ryanodine, normal myotubes still displayed a large Ca2+ transient, whereas no transient was detectable in SkEIIIK-expressing dysgenic myotubes. Collectively, these results indicate that the skeletal muscle L-type channel is a major contributor to the Ca2+ entry attributed to ECCE.
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影响因子：
64.8
作者：
PIETROBON, D;HESS, P
通讯作者：
HESS, P
影响因子：
5.5
作者：
BRUM, G;RIOS, E;STEFANI, E
通讯作者：
STEFANI, E
影响因子：
3.8
作者：
Dirksen, RT;Beam, KG
通讯作者：
Beam, KG
影响因子：
5.5
作者：
Lyfenko, Alla D.;Dirksen, Robert T.
通讯作者：
Dirksen, Robert T.
DOI：
10.1016/0005-2728(72)90194-6
发表时间：
1972-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
ARMSTRONG, CM;BEZANILLA, FM;HOROWICZ, P
通讯作者：
HOROWICZ, P