Role of parvalbumin in fatigue-induced changes in force and cytosolic calcium transients in intact single mouse myofibers.

Role of parvalbumin in fatigue-induced changes in force and cytosolic calcium transients in intact single mouse myofibers.
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小清蛋白在疲劳引起的完整单只小鼠肌纤维中力和胞质钙瞬变变化中的作用。

DOI:
10.1152/japplphysiol.00861.2021
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发表时间:
2022
期刊:
Journal of applied physiology (Bethesda, Md. : 1985)
影响因子:
--
通讯作者:
Hogan,MichaelC
Hogan,MichaelC
中科院分区:
--
文献类型:
--
作者:
Nogueira,Leonardo;Gilmore,NatalieK;Hogan,MichaelC

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小白蛋白(PV)是存在于小鼠快速抽动肌纤维中的最重要的胞浆钙缓冲液之一,而在人类肌纤维中则不存在。之前使用传统PV基因敲除(PV-KO)小鼠的工作表明,终生PVa消融可以提高疲劳抵抗力,这可能是由于线粒体体积的补偿。在本工作中,仅在成年小鼠(PV-KO)中诱导PVAC消融,并在分离的肌肉和完整的单个肌纤维上研究了疲劳过程中的收缩和胞浆钙反应。将结果与对照窝产仔(PV-CTR)进行比较。我们推测,只有在成年PV-KO小鼠中,肌纤维胞浆钙缓冲的减少导致在重复收缩过程中胞浆游离钙浓度([Ca2+]c)更大,从而增强了肌纤维的抗疲劳能力。与PV-CTR相比,PV-KO小鼠指长伸肌在非融合刺激(∼50%,P<0.05)和缓慢松弛(∼46%,P<0.05)中具有更高的力量,但肌肉疲劳抗性或疲劳引起的松弛变化在不同基因型之间没有差异(P>0.05)。在完整的屈指短肌单个肌纤维中,PV-KO在疲劳收缩时的基础和强直性[Ca~(2+)]c高于PV-KO(P<0.05),同时肌浆网(SR)钙泵较PV-CTR肌纤维减慢(∼降低84%,P<0.05),但不同基因型肌纤维的疲劳抗性没有差异(P>0.05)。我们的结果表明,尽管在PV-KO中估计的SR钙摄取被加速,但主要能量消耗者在肌纤维、交叉桥和SR Ca~(2+)ATPase中的总能量需求没有改变到足以影响收缩的能量供应,因此抗疲劳仍然没有受到影响。NEW&NOTEWORTHYPARVALB(PV)是一种胞浆钙缓冲剂,存在于小鼠肌纤维中,而不存在于人肌肉中。我们发现,与对照组相比,可诱导的PVs基因敲除导致疲劳期间肌纤维胞浆游离钙浓度的增加和钙泵的减慢。然而,PVA消融并不干扰疲劳引起的松弛减慢或疲劳抵抗。这些数据支持使用小鼠肌肉作为研究人类肌肉疲劳的合适模型。
One of the most important cytosolic Ca2+buffers present in mouse fast-twitch myofibers, but not in human myofibers, is parvalbumin (PV). Previous work using conventional PV gene (PV) knockout (PV-KO) mice suggests that lifelongPVablation increases fatigue resistance, possibly due to compensations in mitochondrial volume. In this work,PVablation was induced only in adult mice (PV-KO), and contractile and cytosolic Ca2+responses during fatigue were studied in isolated muscle and intact single myofibers. Results were compared with control littermates (PV-Ctr). We hypothesized that the reduced myofiber cytosolic Ca2+buffering developed only in adult PV-KO mice leads to a larger cytosolic free Ca2+concentration ([Ca2+]c) during repetitive contractions, increasing myofiber fatigue resistance. Extensor digitorum longus (EDL) muscles from PV-KO mice had higher force in unfused stimulations (∼50%,P< 0.05) and slowed relaxation (∼46% higher relaxation time,P< 0.05) versus PV-Ctr, but muscle fatigue resistance or fatigue-induced changes in relaxation were not different between genotypes (P> 0.05). In intact single myofibers from flexor digitorum brevis (FDB) muscles, basal and tetanic [Ca2+]cduring fatiguing contractions were higher in PV-KO (P< 0.05), accompanied by a greater slowing in estimated sarcoplasmic reticulum (SR) Ca2+-pumping versus PV-Ctr myofibers (∼84% reduction,P< 0.05), but myofiber fatigue resistance was not different between genotypes (P> 0.05). Our results demonstrate that although the estimated SR Ca2+uptake was accelerated in PV-KO, the total energy demand by the major energy consumers in myofibers, the cross-bridges, and SR Ca2+ATPase were not altered enough to affect the energy supply for contractions, and therefore fatigue resistance remained unaffected.NEW & NOTEWORTHYParvalbumin (PV) is a cytosolic Ca2+buffer that is present in mouse myofibers but not in human muscle. We show that inducible knockout ofPVleads to increases in myofiber cytosolic free Ca2+concentrations and slowing of Ca2+pumping during fatigue versus control mice. However,PVablation does not interfere with fatigue-induced slowing in relaxation or fatigue resistance. These data support the use of mouse muscle as a suitable model to investigate human muscle fatigue.
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