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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Different effects of ATP on the contractile activity of mice diaphragmatic and skeletal muscles.
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Different effects of ATP on the contractile activity of mice diaphragmatic and skeletal muscles.

机译：ATP对小鼠diaphragm肌和骨骼肌收缩活性的不同影响。

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摘要

Apart from acetyl-choline (Ach), adenosine-5'-trisphosphate (ATP) is thought to play a role in neuromuscular function, however little information is available on its cellular physiology. As such, effects of ATP and adenosine on contractility of mice diaphragmatic and skeletal muscles (m. extensor digitorum longa-MEDL) have been investigated in in vitro experiments. Application of carbacholine (CCh) in vitro in different concentrations led to pronounced muscle contractions, varying from 9.15+/-4.76 to 513.13+/-15.4 mg and from 44.65+/-5.01 to 101.46+/-9.11 mg for diaphragm and MEDL, respectively. Two hundred micromolars of CCh in both muscles caused the contraction with the 65% (diaphragm) to 75% (MEDL) of maximal contraction force-this concentration was thus used in further experiments. It was found that application of ATP (100 microM) increased the force of diaphragmatic contraction caused by CCh (200 microM) from 335.2+/-51.4 mg (n=21) in controls to 426.5+/-47.8 mg (n=10; P<0.05), but decreased the contractions of MEDL of CCh from 76.6+/-6.5mg (n=26) in control to 40.2+/-9.0mg (n=8; P<0.05). Application of adenosine (100 microM) had no effect on CCh-induced contractions of these muscles. Resting membrane potential (MP) measurements using sharp electrodes were done at 10, 20 and 30 min after the application of ATP and adenosine. Diaphragm showed depolarization from 75+/-0.6 down to 63.2+/-1.05, 57.2+/-0.96 and 53.6+/-1.1 mV after 10, 20 and 30 min of exposition, respectively (20 fibers from 4 muscles each, P<0.05 in all three cases). Adenosine showed no effect on diaphragmatic MP. Both agents were ineffective in case of MEDL. The effects of ATP in both tissues were abolished by suramin (100 microM), a P2-receptor antagonist, and chelerythrin (50 microM), a specific protein-kinase C (PKC) inhibitor, but were not affected by 1H-[1,2,4]-oxadiazolo-[4,3-alpha]-quinoxalin-1-one (ODQ, 1 microM), a guanylyl-cyclase inhibitor, or by adenosine-3,5-monophosphothioate (Rp-cAMP, 1 microM), a protein-kinase A (PKA) inhibitor. Besides the action on contractile activity, ATP (100 microM) led to a significant (P<0.001) depolarization of diaphragm muscle fibers from 74.5+/-2.3 down to 64+/-2.1, 58.2+/-2.2 and 54.3+/-2.4 mV after 10, 20 and 30 min of incubation, respectively. Incubation of MEDL with the same ATP concentration showed no significant change of MP. Denervation of the muscles for 28 days led to a decrease of CCh-induced contractions of diaphragm down to 171.1+/-34.5mg (n=11, P<0.05), but increased the contractile force of MEDL up to 723.9+/-82.3mg (n=9, P<0.01). Application of ATP elevated the contractility of denervated diaphragm caused by CCh up to normal values (311.1+/-79.7 mg, n=6, P>0.05 versus control), but did not significantly affect of contractility of MEDL, which became 848.1+/-62.7 mg (n=6). These results show that the effects of ATP on both diaphragmatic and skeletal muscles are mediated through P2Y receptors coupled to chelerytrin-sensitive protein-kinase C.
机译：除乙酰胆碱（Ach）外，腺苷5'-三磷酸（ATP）还被认为在神经肌肉功能中起作用，但是关于其细胞生理学的信息很少。这样，已经在体外实验中研究了ATP和腺苷对小鼠diaphragm肌和骨骼肌（长指趾长肌-MEDL）收缩力的影响。体外应用不同浓度的卡巴胆碱（CCh）导致明显的肌肉收缩，,肌和MEDL的变化范围从9.15 +/- 4.76到513.13 +/- 15.4 mg，从44.65 +/- 5.01到101.46 +/- 9.11 mg，分别。两根肌肉中的200微摩尔CCh导致最大收缩力从65％（膜片）到75％（MEDL）收缩，因此该浓度用于进一步的实验。已发现，ATP（100 microM）的使用将CCh（200 microM）引起的diaphragm肌收缩力从对照组的335.2 +/- 51.4 mg（n = 21）增加到426.5 +/- 47.8 mg（n = 10; P <0.05），但将CCh的MEDL收缩从对照组的76.6 +/- 6.5mg（n = 26）降至40.2 +/- 9.0mg（n = 8; P <0.05）。腺苷（100 microM）的使用对CCh诱导的这些肌肉的收缩没有影响。在使用ATP和腺苷后的10、20和30分钟，使用锋利的电极测量静息膜电位（MP）。膜片分别在暴露10、20和30分钟后从75 +/- 0.6下降到63.2 +/- 1.05、57.2 +/- 0.96和53.6 +/- 1.1 mV的去极化（每根4条肌肉的20条纤维，P <在所有三种情况下均为0.05）。腺苷对diaphragm肌MP无影响。两种药物对MEDL均无效。 P2受体拮抗剂苏拉明（100 microM）和特异性蛋白激酶C（PKC）抑制剂白屈菜红素（50 microM）消除了这两种组织中ATP的作用，但不受1H- [1， 2,4] -oxadiazolo- [4,3-α-quinoxalin-1-one（ODQ，1 microM），鸟苷酸环化酶抑制剂或3,5-腺苷单磷酸硫代磷酸酯（Rp-cAMP，1 microM） ，一种蛋白激酶A（PKA）抑制剂。除了对收缩活性的作用外，ATP（100 microM）导致diaphragm肌纤维的显着去极化（P <0.001）从74.5 +/- 2.3降至64 +/- 2.1、58.2 +/- 2.2和54.3 +/-分别孵育10、20和30分钟后为2.4 mV。在相同的ATP浓度下孵育MEDL时，MP无明显变化。 28天的肌肉神经支配导致CCh引起的diaphragm肌收缩下降至171.1 +/- 34.5mg（n = 11，P <0.05），但MEDL的收缩力增加至723.9 +/- 82.3毫克（n = 9，P <0.01）。 ATP的使用可将CCh引起的失神经膜的收缩力提高至正常值（311.1 +/- 79.7 mg，n = 6，相对于对照，P> 0.05），但对MEDL的收缩力没有显着影响，变为848.1 + / -62.7毫克（n = 6）。这些结果表明，ATP对diaphragm肌和骨骼肌的影响是通过P2Y受体与chelerytrin敏感蛋白激酶C偶联介导的。

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