regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion

Definition

Target type: biologicalprocess

Any process that modulates the frequency, rate or extent of cardiac muscle contraction via the regulation of the release of sequestered calcium ion by sarcoplasmic reticulum into cytosol. The sarcoplasmic reticulum is the endoplasmic reticulum of striated muscle, specialised for the sequestration of calcium ions that are released upon receipt of a signal relayed by the T tubules from the neuromuscular junction. [GOC:BHF, GOC:dph, GOC:tb]

The regulation of cardiac muscle contraction is intricately tied to the controlled release and reuptake of calcium ions (Ca2+). Here\\'s a detailed breakdown of this process:

1. **Excitation-Contraction Coupling:**
- The process begins with an action potential arriving at the sarcolemma, the plasma membrane of the cardiac muscle cell (cardiomyocyte).
- This action potential travels down T-tubules, invaginations of the sarcolemma that extend into the cell's interior.
- At the T-tubules, the action potential triggers the opening of voltage-gated L-type calcium channels, allowing a small amount of Ca2+ to enter the cytoplasm from the extracellular space.
- This initial influx of Ca2+ is crucial for triggering the release of a much larger pool of Ca2+ from the sarcoplasmic reticulum (SR), a specialized intracellular organelle responsible for Ca2+ storage.

2. **Calcium-Induced Calcium Release (CICR):**
- The small influx of Ca2+ into the cytoplasm binds to ryanodine receptors (RyRs), Ca2+-sensitive channels located on the SR membrane.
- This binding opens the RyRs, triggering a massive release of Ca2+ from the SR into the cytoplasm. This is known as CICR.

3. **Muscle Contraction:**
- The increased cytoplasmic Ca2+ concentration binds to troponin, a protein complex attached to the thin filament (actin) in the sarcomere, the basic contractile unit of muscle.
- This binding causes a conformational change in troponin, exposing the myosin-binding sites on actin.
- Myosin heads, attached to thick filaments, can now bind to actin, forming cross-bridges.
- The myosin heads then undergo a power stroke, pulling the thin filaments towards the center of the sarcomere, shortening the sarcomere and leading to muscle contraction.

4. **Relaxation:**
- Relaxation occurs when Ca2+ is removed from the cytoplasm, allowing the thin and thick filaments to detach.
- This removal is achieved through:
- The activity of the SR Ca2+-ATPase (SERCA) pump, which actively pumps Ca2+ back into the SR.
- The extrusion of Ca2+ from the cell by the Na+/Ca2+ exchanger (NCX), a membrane protein that exchanges Na+ for Ca2+.

5. **Regulation of Contractility:**
- The force of contraction, known as contractility, is regulated by the amount of Ca2+ released from the SR.
- Factors influencing Ca2+ release and therefore contractility include:
- **Sympathetic nervous system stimulation:** Increases Ca2+ release and contractility by stimulating the release of norepinephrine, which activates β-adrenergic receptors on cardiomyocytes, increasing the activity of SERCA and enhancing the opening of L-type calcium channels.
- **Calcium channel blockers:** Drugs that block L-type calcium channels, reducing Ca2+ influx and decreasing contractility.
- **Cardiac glycosides:** Drugs that increase the contractility of the heart by inhibiting the Na+/K+ ATPase, which indirectly increases intracellular Ca2+ levels.

In summary, the regulation of cardiac muscle contraction involves a complex interplay of Ca2+ release, uptake, and binding to troponin. This process is tightly controlled by various factors and serves as a critical mechanism for regulating heart function and maintaining normal blood circulation.'
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