negative regulation of cardiac muscle cell contraction

Definition

Target type: biologicalprocess

Any process that stops, prevents, or reduces the frequency, rate or extent of cardiac muscle cell contraction. [PMID:19525381]

Negative regulation of cardiac muscle cell contraction is a complex process that involves a coordinated interplay of multiple signaling pathways and molecular mechanisms. The primary aim of this process is to modulate the force and frequency of cardiac muscle contraction, ensuring that the heart functions within a healthy range and adapts to changing physiological demands.

The process initiates with signals from the nervous system or circulating hormones that trigger the activation of specific receptors on the surface of cardiomyocytes. These receptors can be categorized into two major types:

1. **Neurotransmitter receptors:** Receptors for neurotransmitters like acetylcholine (ACh) mediate the parasympathetic nervous system's influence on heart rate. Activation of these receptors triggers the production of second messengers like cyclic adenosine monophosphate (cAMP), ultimately leading to the inhibition of calcium channels in the sarcoplasmic reticulum (SR). This reduced calcium influx weakens the force of contraction.

2. **Hormone receptors:** Receptors for hormones like adrenaline (epinephrine) and noradrenaline (norepinephrine) mediate the sympathetic nervous system's influence on heart rate and contractility. These receptors activate signaling cascades that increase cAMP production, leading to phosphorylation of proteins involved in calcium handling within the cardiomyocytes. This results in enhanced calcium influx and increased contractile force.

Beyond receptor signaling, the negative regulation of cardiac muscle contraction involves several other mechanisms:

1. **Calcium handling**: The process of calcium uptake, storage, and release within the SR is tightly regulated. Proteins like SERCA (sarcoplasmic/endoplasmic reticulum Ca2+-ATPase) pump calcium back into the SR, reducing its concentration in the cytosol and attenuating contraction. Conversely, proteins like phospholamban (PLN) can modulate SERCA activity, affecting calcium handling.

2. **Myofilament interactions**: The interaction between actin and myosin, the proteins responsible for muscle contraction, is regulated by the availability of calcium and the phosphorylation state of regulatory proteins like troponin. By controlling calcium binding and troponin phosphorylation, the heart can fine-tune the interaction between these proteins, thus modulating the strength of contraction.

3. **Cellular energetics**: The energy supply for cardiac muscle contraction is predominantly provided by aerobic metabolism. The negative regulation of contraction can involve mechanisms that reduce energy consumption. This may include altering the activity of enzymes involved in energy production, such as those in the Krebs cycle or electron transport chain.

4. **Mechanical feedback mechanisms**: The heart itself can sense and respond to changes in its workload and contractility. This feedback mechanism allows the heart to adjust its performance in response to altered conditions. For instance, increased heart rate can lead to a decrease in filling time, impacting the contractile force.

Overall, the negative regulation of cardiac muscle cell contraction is a multifaceted process that involves a complex network of signaling pathways, molecular interactions, and cellular adaptations. By orchestrating these processes, the heart ensures its efficient function, adaptability to changing conditions, and long-term health.'
"

Proteins (1)

Compounds (2)