Muscle creatine uptake and creatine transporter expression in response to creatine supplementation and depletion

Abstract

The total creatine pool size [Crtotal; creatine (Cr) + phosphocreatine (PCr)] is crucial for optimal energy utilization in skeletal muscle, especially at the onset of exercise and during intense contractions. The Crtotal likely is controlled by long-term modulation of Cr uptake via the sodium-dependent Cr transporter (CrT). To test this hypothesis, adult male Sprague-Dawley rats were fed 1% Cr, their muscle Crtotal was reduced by ∼85% [1% β-guanidinoproprionic acid (β-GPA)], or their muscle Crtotal was repleted (1% Cr after β-GPA depletion). Cr uptake was assessed by skeletal muscle 14C-Cr accumulation to Cr and PCr by using hindlimb perfusion, and CrT protein content was assessed by Western blot. Cr uptake rate decreased with dietary Cr supplementation in the white gastrocnemius (WG; 45%) only. Depletion of muscle Crtotal to ∼15% of normal increased Cr uptake in the soleus (21%) and red gastrocnemius (22%), corresponding to 70–150% increases in muscle CrT content. In contrast, the inherently lower Cr uptake rate in the WG was unchanged with depletion of muscle Crtotal even though CrT band density was increased by 230%. Thus there was no direct relationship between apparent muscle CrT abundance and Cr uptake rates. However, Cr uptake rates scaled inversely with decreases in muscle Crtotal in the high-oxidative muscle types but not in the WG. This implies that factors controlling Cr uptake are different among fiber types. These observations may help explain the influence of initial muscle Crtotal, time dependency, and variations in muscle Crtotal accumulation during Cr supplementation.

Intake of 13C‐4 creatine enables simultaneous assessment of creatine and phosphocreatine pools in human skeletal muscle by 13C MR spectroscopy

“…Since a 1% increase in TCr with 11% labeled Cr would result in a 10% increase in TCr signal intensity, this indicates that the absolute increase in Cr concentration in the skeletal muscle of our volunteer was somewhat low (1% ± 3%; i.e., (81–70%)/10). Personal factors, including fiber‐type distribution (5, 25), the starting Cr concentration (9), age (19, 26), the so‐called “responsiveness” of the subject (27), and the skeletal muscle examined (11, 12, 28, 29) may all play a role in Cr uptake (see also Ref 3. and references therein).…”

Creatine feeding increases GLUT4 expression in rat skeletal muscle

“…There is considerable evidence that AMPK activation is regulated by phosphorylation of the AMPK ␣-subunit by upstream kinases (AMP kinase kinase) (13,29,30) in total creatine in skeletal muscle over 7 wk of creatine feeding (4). Interestingly, despite no changes in intracellular [creatine], increases in plasma [creatine], and no change in creatine transporter abundance, creatine uptake rates were lowered by ϳ50% in white muscle after the 7 wk of creatine feeding (4). This suggests that, during creatine feeding, some factor other than tissue total creatine content can affect muscle physiology.…”

The chick embryo rules (still)!

“…After creatine supplementation the levels of TCr were similar in both strains (Table 1): TCr increased by 12% in muscles of mdx mice and remained unchanged in C57 animals. A lack of TCr increase in EDL muscle of C57 mice has been reported previously 4, 7, 23. Recently, Brault et al4 showed that, after creatine depletion by guanidinopropionic acid (GPA), the rate of creatine uptake was related to fiber type and independent of the level of creatine reached.…”