右心不全ラットにおける骨格筋筋小胞体のCa2+取り込み能およびSERCA発現について

右心不全に伴って,速筋および遅筋の筋小胞体Ca2+取り込み能が減少するという仮説を検証した.右心不全は,モノクロタリン(30 ㎎/㎏)を投与することにより引き起こし,投与後4週で,長指伸筋およびヒラメ筋を両後肢から採取した.筋の疲労耐性は,連続的な強縮刺激を行うことにより測定した.長指伸筋では刺激開始1分後,ヒラメ筋では4分後の張力を測定し,初期値に対するそれらの割合を疲労の指標とした.長指伸筋およびヒラメ筋の疲労耐性は,右心不全群で有意に低下した.筋小胞体Ca2+取り込み速度は,Indo-Ⅰを付加したホモジネートで測定した.その結果,Ca2+取り込み速度は,長指伸筋で25.4%(p<0.01),ヒラメ筋で30.4%(p<0.05)低下した.このCa2+取り込み速度の低下は,筋小胞体Ca2+-ATPaseタンパク量の低下と一致した.筋小胞体Ca2+取り込み能の低下は,筋張力の低下を引き起こし,このCa2+ handlingの低下は,少なくとも右心不全による運動耐容能の低下の一因であろう.

In this study, we investigated the hypothesis that right congestive heart failure (CHF) would impair sarcoplasmic reticulum (SR) Ca2+ uptake in skeletal fast- and slow-twitch muscles. To induce CHF, the rats were injected with monocrotalin (30 ㎎/㎏). After 4 weeks of injection, extensor digitorum longus (EDL) and soleus (SOL) muscles were sampled from both hind limbs. Muscle fatigue resistance was measured in vitro as the relative decline in force production of tetanic contraction induced by electrical stimulation over 1 and 4 min in EDL and SOL, respectively. Evaluation of fatigue characteristics showed that CHF significantly reduced fatigue resistance in both muscles under study.SR Ca2+uptake rate wasmeasured in vitro with Indo-I on muscle homogenates. As hypothesized, Ca2+uptake rate was decreasedby 25.4%(P < 0.01) and 30.4%(P < 0.05) in EDL and SOL, respectively. This decline in Ca22+uptake ratewas accompanied by an immunochemically determined decrease in SR Ca2+-ATPase protein. Taking intoaccount previous findings that the depressed SR Ca2+uptake leads to the reduce in muscle forceproduction, these results suggest that impaired SR Ca2+handling capacity in skeletal muscle may accountat least partly for deteriorations in exercise tolerance resulting from right CHF.