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. 2021 Sep 28;22(19):10444.
doi: 10.3390/ijms221910444.

Role of Pannexin 1 ATP-Permeable Channels in the Regulation of Signaling Pathways during Skeletal Muscle Unloading

Ksenia A Zaripova  1 , Ekaterina P Kalashnikova  1 , Svetlana P Belova  1 , Tatiana Y Kostrominova  2 , Boris S Shenkman  1 , Tatiana L Nemirovskaya  1
Affiliations

Role of Pannexin 1 ATP-Permeable Channels in the Regulation of Signaling Pathways during Skeletal Muscle Unloading

Ksenia A Zaripova et al. Int J Mol Sci. .

Abstract

Skeletal muscle unloading results in atrophy. We hypothesized that pannexin 1 ATP-permeable channel (PANX1) is involved in the response of muscle to unloading. We tested this hypothesis by blocking PANX1, which regulates efflux of ATP from the cytoplasm. Rats were divided into six groups (eight rats each): non-treated control for 1 and 3 days of the experiments (1C and 3C, respectively), 1 and 3 days of hindlimb suspension (HS) with placebo (1H and 3H, respectively), and 1 and 3 days of HS with PANX1 inhibitor probenecid (PRB; 1HP and 3HP, respectively). When compared with 3C group there was a significant increase in ATP in soleus muscle of 3H and 3HP groups (32 and 51%, respectively, p < 0.05). When compared with 3H group, 3HP group had: (1) lower mRNA expression of E3 ligases MuRF1 and MAFbx (by 50 and 38% respectively, p < 0.05) and MYOG (by 34%, p < 0.05); (2) higher phosphorylation of p70S6k and p90RSK (by 51 and 35% respectively, p < 0.05); (3) lower levels of phosphorylated eEF2 (by 157%, p < 0.05); (4) higher level of phosphorylated GSK3β (by 189%, p < 0.05). In conclusion, PANX1 ATP-permeable channels are involved in the regulation of muscle atrophic processes by modulating expression of E3 ligases, and protein translation and elongation processes during unloading.

Keywords: MAFbx; MuRF1; muscle unloading; pannexin channel 1.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Evaluation of the ATP content (A) and Panx1 mRNA expression (B,C) in soleus muscles of non-treated control rats (1C and 3C), rats after 1 and 3 days of unloading (1HS and 3HS), and 1 and 3 days of HS with PRB inhibitor (1HP and 3HP). Levels of Panx1 mRNA were normalized to the levels of Gapdh in each sample (B,C). n = 8. * indicates a significant difference from the control, # indicates a significant difference from the HS group, p < 0.05.
Figure 2
Figure 2
Evaluation of the MuRF1 (A,B) and MAFbx (C,D) mRNA expression in soleus muscles of non-treated control rats (1C and 3C), rats after 1 and 3 days of unloading (1HS and 3HS), and 1 and 3 days of HS with PRB inhibitor (1HP and 3HP). Levels of MuRF1 and MAFbx mRNA were normalized to the levels of Gapdh in each sample. n = 8. * indicates a significant difference from the control, # indicates a significant difference from the HS group, p < 0.05.
Figure 3
Figure 3
Evaluation of the MYOG (A), p-FoxO3 (B) and p-AKT (C) content in soleus muscles of non-treated control rats (1C and 3C), rats after 1 and 3 days of unloading (1HS and 3HS), and 1 and 3 days of HS with PRB inhibitor (1HP and 3HP). Values are normalized to the level of GAPDH (A), total FoxO3 (B) and total Akt (C) in each sample. n = 8. * indicates a significant difference from the control, # indicates a significant difference from the HS group, p < 0.05.
Figure 4
Figure 4
Evaluation of the p-eEF2 (A), p-p70S6K (B) and p-p90RSK (C) content in soleus muscles of non-treated control rats (1C and 3C), rats after 1 and 3 days of unloading (1HS and 3HS), and 1 and 3 days of HS with PRB inhibitor (1HP and 3HP). Values are normalized to the level of total eEF2 (A), total p70S6K (B) and total p90RSK (C) in each sample. n = 8. * indicates a significant difference from the control, # indicates a significant difference from the HS group, p < 0.05.
Figure 5
Figure 5
Evaluation of the p-GSK3b (A), p-ERK1/2 (B) and p-AMPK (C) content in soleus muscles of non-treated control rats (1C and 3C), rats after 1 and 3 days of unloading (1HS and 3HS), and 1 and 3 days of HS with PRB inhibitor (1HP and 3HP). Values are normalized to the level of total GSK3b (A), total ERK1/2 (B) and total AMPK (C) in each sample. n = 8. * indicates a significant difference from the control, # indicates a significant difference from the HS group, p < 0.05.
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