低酸素収縮機能障害におけるCa2(+) 依存メカニズムとCa2(+) 独立メカニズムの相対的な役割
1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Circulation
|August 1, 1990
まとめ
低酸素性心不全は,低カルシウムレベルが原因ではない. 代わりに,無機リン酸 (Pi) の蓄積と,より少量の酸性により,低酸素期間の心臓筋収縮が損なわれます.
科学分野:
- 心血管生理学 心血管の生理学
- メタボリック・レギュレーション
- カルディアック・エナジェティクス
背景:
- 心臓の収縮機能不全は,低酸素と代謝抑制の既知の結果です.
- 正確なメカニズムは,アクティベーターカルシウムの減少または阻害代謝産物の蓄積によるものかどうか,まだ議論されています.
研究 の 目的:
- 細胞内カルシウム ([Ca2+]i) と無機リン酸 ([Pi]) が,低酸素収縮機能障害において果たす役割を区別する.
- 低酸素期における心臓機能に対する細胞内pH (pHi) の影響を調査する.
主な方法:
- 使用済みのペルファージドフレットハートは,制御された低酸素状態 (10% O2) に置かれました.
- フッ素-19 NMRを含む核磁気共振 (NMR) スペクトロスコピーを用いて[Ca2+]i,[Pi],およびpHiを測定した.
- 収縮機能を評価するための量化された左心室発達圧 (LVDP).
主要な成果:
- 低酸素症は,LVDPをコントロール値の約60%まで低下させた.
- NMRは,低酸素期における[Pi]の増加と軽度の細胞内酸性酸化 (pHiの減少) を明らかにした.
- 増加した[Pi]と減少したpHiの両方とも,減少したLVDPと相関しており, [Pi]が支配的な影響を及ぼしている.
- ダイアストールの終了時の[Ca2+]iは変化せず,ピークシストリック[Ca2+]iは逆説的に増加した;Ca2+の一時的な振幅は圧力低下と相関しなかった.
結論:
- 軽度の安定状態の低酸素症における収縮性不全は,主に無機リン酸 ([Pi]) の蓄積によって媒介されます.
- 細胞内アシドーシス (H+の蓄積) も[Pi]に寄与するが,下酸素機能障害を引き起こすのは[Pi]に次要である.
- アクティベーターカルシウム ([Ca2+]i) の可用性または調節の低下は,これらの条件下で収縮障害の主な原因ではありません.
関連する概念動画
01:26Cross-bridge Cycle
As muscle contracts, the overlap between the thin and thick filaments increases, decreasing the length of the sarcomere—the contractile unit of the muscle—using energy in the form of ATP. At the molecular level, this is a cyclic, multistep process that involves binding and hydrolysis of ATP, and movement of actin by myosin.
01:10The Role of Actin and Myosin in Non-muscle Cells
Actin and myosin or actomyosin filaments also play a significant role in cells other than those involved in muscle contraction (which occurs within the sarcomere of muscle cells). The mechanism of non-muscle cell contractile bundles was first observed in Dictyostelium and Acanthamoeba. In non-muscle cells, two bundles are commonly found: stress fibers and actomyosin adherence belts. These contractile bundles are smaller and less organized than the ones found in muscle cells. They are held...
01:16Calmodulin-dependent Signaling
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
01:29Relaxation of Skeletal Muscles
The period of muscle contraction primarily influences the duration of stimulation at the neuromuscular junction (NMJ), the presence of free calcium ions in the sarcoplasm, and the availability of energy or ATP to support contractions.
When an action potential reaches the axon terminal, it depolarizes the membrane and opens voltage-gated sodium channels. Sodium ions enter the cell, further depolarizing the presynaptic membrane. This depolarization causes voltage-gated calcium channels to open.
When an action potential reaches the axon terminal, it depolarizes the membrane and opens voltage-gated sodium channels. Sodium ions enter the cell, further depolarizing the presynaptic membrane. This depolarization causes voltage-gated calcium channels to open.
01:25Smooth Muscle Contraction
Smooth muscle contraction is a complex process vital for various bodily functions, from maintaining blood vessel tension to facilitating the movement of food through the digestive tract. Unlike striated muscles, smooth muscle contraction begins more slowly and lasts longer.
The onset of contraction is triggered by an increase in calcium ions within the sarcoplasm, similar to the process in striated muscle. However, smooth muscles have a relatively smaller reservoir of the sarcoplasmic...
The onset of contraction is triggered by an increase in calcium ions within the sarcoplasm, similar to the process in striated muscle. However, smooth muscles have a relatively smaller reservoir of the sarcoplasmic...
01:29Pathophysiology of Cardiac Performance
Typical heart performance is influenced by heart rate, rhythm, myocardial contraction, and metabolism or blood flow. The cardiac muscle exhibits distinct electrophysiological features, including pacemaker activity and calcium channel control, which play a vital role in the heart's response to various drugs. The autonomic nervous system, comprising the sympathetic and parasympathetic branches, regulates heart rate. Sympathetic activation increases heart rate, while parasympathetic activation...