心臓循環による心筋細胞メカニカルトランスデュークションの調節
K Yamamoto1, Q N Dang, Y Maeda
1Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Circulation
|March 14, 2001
まとめ
心循環中の機械的ストレスは,特定の信号伝達経路を活性化します. この細胞のメカニカルトランスデュークションは,圧力と体積の過負荷が心臓の形態学にどのように異なる影響を与えるかを説明するかもしれない.
科学分野:
- 心臓病学 心臓病学
- 分子生物学は分子生物学である.
- バイオフィジックス 生物物理学
背景:
- 左心室の圧力過負荷 (シストリック) と体積過負荷 (ダイアストリック) は,異なる形態学的反応を引き起こす.
- これらの反応の背後にある細胞メカニズムを理解することは,心臓の健康にとって極めて重要です.
研究 の 目的:
- 心循環の異なる段階における機械的なストレスが,心臓筋細胞のシグナル伝達と遺伝子発現にどのように影響するか調査する.
- 心循環のタイミングが,機械的ストレスに対する細胞の反応に影響するかどうかを判断する.
主な方法:
- 新しいコンピュータ制御システムでは,特定の心循環段階 (シストリック対ダイアストリック) で心筋細胞に双軸的ストレスを加えた.
- ミトゲン活性化タンパク質キナーゼ (MAPK) 経路 (p44/42,p38,JNK) と遺伝子/タンパク質合成の測定された活性化.
主要な成果:
- シストリック株は選択的にp44/42 MAPKとMAPK/細胞外信号調節タンパク質キナーゼキナーゼ (MEK1/2) を活性化させ,ダイアストリック株と比較した.
- 脳内ナトリウレティックペプチドとテンアシン-C mRNAの発現は,シストリックストレンの場合,著しく高かった.
- タンパク質合成は, [(3) H]レウシンの組み込みによって測定され,シストリックストレスの場合より大きく,MEK1/2阻害剤によって抑制されました.
結論:
- p44/42 MAPK/MEK1/2の機械的活性化,遺伝子発現,タンパク質合成は心臓循環によって調節される.
- 特定のサイクルフェーズ中の心臓のメカニカルトランスデュークションは,心臓に対する圧力と体積の過負荷の差異的な効果を裏付けている可能性があります.
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.
01:13The Cardiac Cycle
The heart beats rhythmically in a sequence called the cardiac cycle—a rapid coordination of contraction (systole) and relaxation (diastole).
The Process
Electrical signals—sent from the sinoatrial (SA) node in the right atrial wall to the atrioventricular (AV) node between the right atrium and right ventricle—cause both atria to simultaneously contract. When the signal reaches the AV node, it pauses for approximately a tenth of a second, allowing the atria to contract and empty blood into the...
The Process
Electrical signals—sent from the sinoatrial (SA) node in the right atrial wall to the atrioventricular (AV) node between the right atrium and right ventricle—cause both atria to simultaneously contract. When the signal reaches the AV node, it pauses for approximately a tenth of a second, allowing the atria to contract and empty blood into the...
01:27Feedback Regulation of Calcium Concentration
Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
01:27Specialized Characteristics of Cardiac Muscles
The primary role of cardiac muscles is to propel blood throughout the cardiovascular system. The cardiac muscle cells, or cardiomyocytes, exhibit specialized characteristics that allow them to perform this function.
Cardiac muscle cells are smaller than skeletal muscles, averaging 10–20 mm in diameter and 50–100 mm in length. However, they have large energy demands for continuous contraction and relaxation. This energy is almost exclusively derived from aerobic metabolism of energy reserves in...
Cardiac muscle cells are smaller than skeletal muscles, averaging 10–20 mm in diameter and 50–100 mm in length. However, they have large energy demands for continuous contraction and relaxation. This energy is almost exclusively derived from aerobic metabolism of energy reserves in...
01:19Electrophysiology of Normal Cardiac Rhythm
The normal cardiac rhythm is a synchronized electrical activity that facilitates the regular and coordinated contraction of the heart muscle. This process is essential for efficient blood circulation throughout the body. The fundamental elements involved in establishing and maintaining this rhythm include the unique electrical properties of cardiac muscle cells, the sinoatrial (SA) node's pacemaker function, the specialized conducting system, and the ionic mechanisms underlying each phase of...
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...