Physiological role of Kvß2 (AKR6) in murine skeletal muscle growth and regulation.

AIM: Potassium channel accessory subunits (Kvß) play a key role in cardiac electrical activity through ion channel modulation. In this study, we hypothesize that Kvß2 regulates skeletal muscle growth and fibre phenotype via protein-protein interactions. METHODS: Kvß2 knockout mouse model was used for morphometric, immunohistochemical and biochemical analysis to evaluate the role of Kvß2 in skeletal muscle physiology. RESULTS: Deletion of Kvß2 gene in mice (Kvß2 knockout, KO) leads to significant decrease in body weight along with skeletal muscle size. Key hindlimb muscles such as biceps, soleus and gastrocnemius were significantly smaller in size in KO mice compared to that of wild type. Morphometric measurements and histological analysis clearly point that the fibre size is decreased in each of the muscle type in KO compared with wild-type mice. In addition, Kvß2 deletion contributes to fibre-type switching from fast to slow fibre as indicated by more abundant MHCI-expressing fibres in gastrocnemius and soleus muscles, which may underscore the smaller muscle size alongside increase in U3 ubiquitin ligase; NEDD4 expression. Using targeted siRNA knockdown approach, we identified that Kvß2 knockdown does not affect the myoblasts proliferation. However, Pax7 expression was significantly decreased in 4-week-old gastrocnemius muscle, suggesting that cellular reserve for growth may be deficient in KO mice. This is further supported by decreased migratory capacity of C2C12 cells upon siRNA-targeted Kvß2 knockdown. CONCLUSION: Overall, this is the first report identifying that genetic deletion of Kvß2 leads to decreased skeletal muscle size along with isotype switching.

An examination of the association of serum IGF-I concentration, potential candidate genes, and fiber type composition with variation in residual feed intake in progeny of Red Angus sires divergent for maintenance energy EPD.

Investigating the genetic and physiological drivers of postweaning residual feed intake (RFI) and finishing phase feed efficiency (FE) may identify underlying mechanisms that are responsible for the variation in these complex FE traits. The objectives were 1) to evaluate the relationship of serum IGF-I concentration and muscle gene expression with postweaning RFI and sire maintenance energy (MEM) EPD and 2) to determine fiber type composition as it relates to postweaning RFI and finishing phase FE. Results indicate that RFI and serum IGF-I concentration were not associated (P > 0.05); however, negative correlations (P < 0.05) between sire MEM EPD and serum IGF-I concentration were observed. Gene expression differences between high- and low-RFI animals were observed in cohort 1, where IGFBP5 expression was greater (P < 0.05) in high-RFI animals. When animals were grouped according to sire MEM EPD, the low MEM EPD group of cohort 1 showed greater muscle mRNA expression (P < 0.01) of fatty acid synthase (FASN) and marginally (P < 0.10) greater expression of IGFBP5 and C/EBP alpha (C/EBPα) whereas the high MEM EPD group of cohort 2 had greater muscle mRNA expression of IGFBP2 (P < 0.05) and C/EBPα (P ≤ 0.01) and marginally (P < 0.10) greater expression of IGFBP3. Biopsy tissue samples collected at harvest revealed that the percentage of type IIa fibers was lower (P ≤ 0.05) in high-RFI steers, with a similar trend (P < 0.10) being observed in high finishing phase FE steers. The percentage of type IIb fibers was higher (P < 0.05) in high-RFI (and finishing phase FE) steers than in low-RFI (and finishing phase FE) steers. There was a marginal, negative correlation between RFI and type I (r = -0.36, P = 0.08) and IIa (r = -0.37, P = 0.07) fiber percentages and a positive correlation (r = 0.48, P = 0.01) between RFI and type IIb fiber percentage whereas finishing phase FE was negatively correlated (r = -0.43, P = 0.03) with type I fiber percentage and positively correlated (r = 0.44, P = 0.03) with type IIb fiber percentage. Therefore, our data indicate that 1) serum IGF-I (collected at weaning) is not an indicator of postweaning RFI, 2) the GH-IGF axis appears to have some involvement with RFI at the molecular level; however, muscle gene expression results were not consistent across cohorts, and 3) low-RFI animals may have the ability to more efficiently maintain and accrete muscle mass due to their fiber type composition, specifically a greater proportion of type I fibers.