Changes Of Sarcolemmai Ion Channels In Unloaded Soleus And Their Functional Roles

Weightlessness or simulated weightlessness has been shown to cause atrophy, to reduce contraction function, and to increase fatigability in rat hindlimb skeletal muscles. With the development of space exploration projects, the atrophy and decreased function in antigravity skeletal muscles are one of major problems that need to be solved for the prolonged space flight. To understand the features of decreased contractile function and increased fatigability in unloaded hindlimb skeletal muscles will help to develop effective countermeasures during space flight, and contribute to the prevention and treatment of skeletal muscle atrophy in long-term bed-rest patients.The increase in fatigability of high-frequency tetanic contraction in unloaded soleus (SOL) may be related to the changes in sarcolemmal Na+, K+, or L-type Ca2+ channels and Na+-K+ ATPase. During soleus exposing to high-frequency stimulation, potassium ions accumulation and sodium ions exhausting areformed rapidly in T-tubule. The ion concentration alterations in T-tubule lead to a depolarization block of T-tubular action potential, then inhibit the function of L-type Ca2+ channels. The mRNA expression of L type calcium channel in T-tubular membrane may increase due to the compensation for its functional decrease. Elevation of intracellular calcium ions may be partly induced by increased influx through sarcolemma L type-calcium channels. Intracellular calcium elevation, on one hand, would activate calpain, a calcium- dependent cysteine protease that degrade the myofibrillar proteins and cause muscle atrophy; on the other hand, result in activation of calcineurin which enhance the activity of MHC I promoter and inhibit a shift of MHC isoforms from slow to fast in soleus.In order to test the above working hypothesis, the contractile functions in unloaded soleus were observed by using in vitro skeletal muscle strip perfusion, the expression of MHC proteins and mRNA was detected by SDS-PAGE and RT-PCR, respectively. The results and findings are as follows:1) Set up a tail-suspended mouse model.2) Marked atrophy in 1 week of tail-suspended mouse soleus The ratio of SOL weight/body weight(BW) decreased by 45.26 2.72 % in one week tail-suspended (SUS) mice, and the same reduction was observed in one week SUS rat soleus(45.45 1.79 %). The CSA of SOL in 1 week SUS was significantly lower than that in control (CON) (CON 1.03 0.04 vs. SUS 0.69 0.02 mm2, P<0.01). The length of SOL didn't change.3) Shortened twitch duration in unloaded soleus The isometric maximal twitch tension (Pt) and resting tension (RT) had no changein SOL after one week of unloading. However, the time to peak tension (TPT) of twitch contraction showed significant shortening from 58.34 1.02 ms in CON to 46.57 1.49 ms in unloaded soleus after one week SUS (P<0.01). The time from peak tension to 75 % relaxation (TR75) was not significantly changed (CON 66.8 + 2.47 vs. SUS 63.89 2.64 ms, P>0.05)4) Increased fatigability after 1-wk unloaded soleus during high-frequency tetanic contraction In high-frequency tetanic contraction, the maximal tension (Po) of SOL had no change after one week of SUS, only decreased by 7% as compared to CON (P>0.05). The tension at the thirty-third second of tetanic contraction (P33) dropped 64.68 1.94 % as compared to Po in one week of unloaded soleus in contrast to 74.21 1.15 % drop in control (P<0.01). This represents an increase in fatigability of high-frequency titanic contraction in one week of unloaded soleus.5) Faster recovery of tetanic tension after fatigue after 1-wk unloaded soleus After tetanic contraction, the restored time was shortened in 1 week SUS group (CON 25.71 0.78 vs. SUS 11.87 1.26min, P<0.01).6) Increased fatigability of titanic contraction after 1-wk unloaded soleus with high potassium perfusion With 10 mmol/L K+ solution perfusion, there was no differenc in Po between CON and 1 week SUS, but the P33/Po shown a significant increa...