Oscillating calcium signals in smooth muscle cells underlie the persistent basal tone of internal anal sphincter.
Oscillating calcium signals in smooth muscle cells underlie the persistent basal tone of internal anal sphincter.
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DOI：
10.1002/jcp.30279
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发表时间：
2021-08
影响因子：
5.6
通讯作者：
ZhuGe R
中科院分区：
文献类型：
--
作者：
Lu P;Chen J;Zhang C;Saur D;Baer CE;Lifshitz LM;Fogarty KE;ZhuGe R
内肛门括约肌（IAS）持续的基底张力对于保持肛管闭合和大便控制是必不可少的。它通过直肠抑制反射（RAIR）的抑制是成功排便所必需的。然而，IAS基底音的细胞信号仍然是一个谜。在这里，我们报告了钙信号的起源和分子机制，控制IAS基底音调，使用组合方法，包括一种新的IAS切片制备，在体内保留细胞排列和结构，双光子成像和细胞特异性基因修饰小鼠。我们发现IAS平滑肌细胞产生两种形式的收缩（即阶段性和持续收缩）和Ca2+信号（即同步Ca2+振荡（SCaOs）和异步Ca2+振荡（ACaOs）），持续数小时。RyRs, TMEM16A， l型Ca2+通道和间隙连接是SCaOs所必需的，它们占阶段性收缩和持续收缩的75%。然而，acao只需要ryr，它们贡献了25%的持续收缩。一氧化氮，主要的神经递质，介导RAIR，阻断两种类型的Ca2+信号，导致IAS的完全放松。我们的研究结果表明，Ca2+信号的振荡性质产生并维持了基底张力，而不会对IAS造成细胞毒性。我们的研究提供了对大便失禁和正常排便的见解。
A persistent basal tone in the internal anal sphincter (IAS) is essential for keeping the anal canal closed and fecal continence. Its inhibition via the rectoanal inhibitory reflex (RAIR) is required for successful defecation. However, cellular signals underlying the IAS basal tone remain enigmatic. Here we report the origin and molecular mechanisms of calcium signals that control the IAS basal tone, using a combination approach including a novel IAS slice preparation that retains cell arrangement and architecture as in vivo, 2-photon imaging, and cell-specific gene-modified mice. We found that IAS smooth muscle cells generate two forms of contractions (i.e., phasic and sustained contraction) and Ca2+ signals (i.e., synchronized Ca2+ oscillations (SCaOs) and asynchronized Ca2+ oscillations (ACaOs)) that last for hours. RyRs, TMEM16A, L-type Ca2+ channels, and gap junctions are required for SCaOs, which account for phasic contraction and 75% of sustained contraction. Nevertheless, only RyRs are required for ACaOs, which contribute 25% of sustained contraction. Nitric oxide, the primary neurotransmitter mediating the RAIR, blocks both types of Ca2+ signals, leading to IAS’s full relaxation. Our results show that the oscillating nature of Ca2+ signals generates and maintains the basal tone without causing cytotoxicity to IAS. Our study provides insight into fecal continence and normal defecation.
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影响因子：
2.9
作者：
KRUMDIECK, CL;DOSSANTOS, JE;HO, KJ
通讯作者：
HO, KJ
影响因子：
5.5
作者：
Gao, Ning;Chang, Audrey N.;Stull, James T.
通讯作者：
Stull, James T.
DOI：
10.1152/ajplung.1997.272.1.l1
发表时间：
1997-01-01
影响因子：
4.9
作者：
Kannan, MS;Prakash, YS;Sieck, GC
通讯作者：
Sieck, GC
影响因子：
5.5
作者：
Hall, K. A.;Ward, S. M.;Keef, K. D.
通讯作者：
Keef, K. D.
DOI：
10.1152/ajplung.00494.2005
发表时间：
2006-08-01
影响因子：
4.9
作者：
Bai, Yan;Sanderson, Michael J.
通讯作者：
Sanderson, Michael J.