Mechanical regulation of native and the recombinant calcium channel.
Mechanical regulation of native and the recombinant calcium channel.
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DOI：
10.1016/j.ceca.2012.12.007
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发表时间：
2013-04
期刊：
影响因子：
4
通讯作者：
Morad M
中科院分区：
文献类型：
--
作者：
Rosa AO;Yamaguchi N;Morad M
L型钙通道受电压、钙离子（Ca 2+依赖性失活和易化）、胞质蛋白（CAM、CAMKII、PKA、PKC等）和氧自由基等多种机制调节。在这里，我们描述了另一种Ca 2+通道调节机制，该机制由约25 dyn/cm 2的压力-流动（PF）力诱导，产生35-60%的通道电流抑制。仅需要短周期（300 ms）的这种PF脉冲来可逆地抑制电流。在HEK 293细胞中表达的重组Ca 2+通道（α 1c 77/β2a/α2δ和α 1c 77/β1/α2δ）被PF脉冲类似地抑制。为了检查由PF脉冲触发的不同亚细胞隔室（SR、ER、线粒体）释放的Ca 2+是否是PF对通道电流的抑制作用的基础，采用药理学试剂和离子取代来探测这种可能性。在对照细胞和暴露于U 73122和2-APB（PLC和IP 3R通路调节剂）、毒胡萝卜素和BAPTA（SERCA 2a调节剂）、二硝基苯酚、FCCP和Ru 360（线粒体抑制剂）、L-NAMME（NOS抑制剂信号传导）、cAMP和百日咳毒素（Gi蛋白调节剂）的那些细胞之间，未发现PF脉冲抑制伊卡或IBa（用于抑制CICR）的有效性的显著差异。我们的结论是，快速和可逆的调制的Ca 2+通道的PF脉冲是独立的细胞内释放的Ca 2+和Ca 2+依赖的通道失活，并可能代表直接的机械调节作用的通道蛋白除了以前报道的Ca 2+释放或进入依赖的机制。
L-type calcium channels are modulated by a host of mechanisms that include voltage, calcium ions (Ca2+ dependent inactivation and facilitation), cytosolic proteins (CAM, CAMKII, PKA, PKC, etc), and oxygen radicals. Here we describe yet another Ca2+ channel regulatory mechanism that is induced by pressure-flow (PF) forces of ~25 dyn/cm2 producing 35–60% inhibition of channel current. Only brief periods (300ms) of such PF pulses were required to suppress reversibly the current. Recombinant Ca2+ channels (α1c77/β2a/α2δ and α1c77/β1/α2δ), expressed in HEK293 cells, were similarly suppressed by PF pulses. To examine whether Ca2+ released by PF pulses triggered from different sub-cellular compartments (SR, ER, mitochondria) underlies the inhibitory effect of PF on the channel current, pharmacological agents and ionic substitutions were employed to probe this possibility. No significant difference in effectiveness of PF pulses to suppress ICa or IBa, (used to inhibit CICR), was found between control cells and those exposed to U73122 and 2-APB (PLC and IP3R pathway modulators), thapsigargin and BAPTA (SERCA2a modulator), dinitrophenol, FCCP and Ru360 (mitochondrial inhibitors), L-NAMME (NOS inhibitor signaling), cAMP and Pertussis toxin (Gi protein modulator). We concluded that the rapid and reversible modulation of the Ca2+ channel by PF pulses is independent of intracellular release of Ca2+ and Ca2+ dependent inactivation of the channel and may represent direct mechanical regulatory effect on the channel protein in addition to previously reported Ca2+-release or entry dependent mechanism.
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影响因子：
20.1
作者：
Iribe G;Ward CW;Camelliti P;Bollensdorff C;Mason F;Burton RA;Garny A;Morphew MK;Hoenger A;Lederer WJ;Kohl P
通讯作者：
Kohl P
影响因子：
3
作者：
Birnbaumer, L;Qin, N;Stefani, E
通讯作者：
Stefani, E
影响因子：
5.5
作者：
CLEEMANN, L;MORAD, M
通讯作者：
MORAD, M
影响因子：
20.1
作者：
Hool, LC
通讯作者：
Hool, LC
影响因子：
3.5
作者：
Amano, S;Ishikawa, T;Nakayama, K
通讯作者：
Nakayama, K