What regulates the contraction of heart muscle?

Regulation of Heart Muscle Contraction

Heart muscle contraction is primarily regulated by the autonomic nervous system (sympathetic and parasympathetic divisions) and calcium ions, with additional modulation by intrinsic cardiac mechanisms, hormonal factors, and local metabolic conditions.

Autonomic Nervous System Regulation

The heart is under constant influence of both sympathetic and parasympathetic nervous systems, which work in opposition to maintain cardiac homeostasis 1:

Parasympathetic (Vagal) Control

• Origin: Nucleus ambiguus and dorsal motor nucleus in the brainstem
• Effects: Inhibitory to heart function
• Speed: Rapid onset and decay (within one heartbeat)
• Primary neurotransmitter: Acetylcholine
• Actions:
  • Decreases heart rate
  • Reduces conduction velocity through AV node
  • Decreases contractile force (primarily atrial)

Sympathetic Control

• Origin: Reticular formation in the brainstem with postganglionic neurons
• Effects: Facilitatory to heart function
• Speed: Slower onset and decay (multiple heartbeats)
• Primary neurotransmitter: Norepinephrine
• Actions:
  • Increases heart rate
  • Enhances conduction velocity
  • Increases contractile force
  • Dilates coronary vessels

Cellular and Molecular Mechanisms

Calcium Regulation

Calcium ions (Ca²⁺) are the primary direct mediators of cardiac muscle contraction 1:

1. Excitation-Contraction Coupling:

   • Depolarization opens voltage-dependent L-type calcium channels
   • Ca²⁺ enters cardiomyocytes, triggering calcium-induced calcium release from sarcoplasmic reticulum
   • Released Ca²⁺ binds to troponin C, enabling actin-myosin interaction and contraction

2. β-adrenergic Stimulation (sympathetic):

   • Activates β-adrenergic receptor/cAMP/PKA pathway
   • Increases calcium influx through L-type channels
   • Enhances sarcoplasmic reticulum calcium release
   • Accelerates calcium reuptake during relaxation

3. Parasympathetic Effects:

   • Inhibits cAMP formation
   • Reduces calcium influx
   • Decreases contractility

Intrinsic Cardiac Nervous System

The heart possesses its own nervous system that can function independently 1:

• Consists of afferent, efferent, and local circuit neurons
• Located in ganglionated plexi on the heart
• Integrates signals and ensures appropriate heart function even with focal lesions

Factors Affecting Cardiac Contractility

Preload and Afterload

• Frank-Starling Mechanism: Increased venous return (preload) stretches cardiac muscle, increasing contractile force
• Afterload: Resistance against which the heart must pump affects contractility

Hormonal Regulation

• Renin-Angiotensin-Aldosterone System (RAAS):

  • Angiotensin II increases contractility directly via AT1 receptors
  • Stimulates release of aldosterone and catecholamines
  • Promotes cardiac hypertrophy through growth factor expression 1

• Catecholamines (epinephrine, norepinephrine):

  • Increase heart rate and contractility
  • Released during stress or exercise

Metabolic Factors

• Oxygen supply: Myocardial ischemia impairs contractility
• pH: Acidosis decreases contractility
• Electrolytes: Potassium, calcium, and magnesium levels affect contractility

Pathophysiological Considerations

Diastolic Dysfunction

Impaired relaxation of heart muscle can result from 1:

• Delayed inactivation due to abnormal calcium reuptake
• Increased chamber stiffness from hypertrophy
• Myocardial ischemia affecting relaxation

Myocardial Ischemia

Compromised blood flow affects contractility through 1:

• Supply-demand mismatch
• Impaired calcium handling
• Altered metabolic state of cardiomyocytes

Pharmacological Modulation

Cardiac contractility can be modified by medications:

• Positive inotropes like milrinone increase contractility by inhibiting phosphodiesterase, increasing cAMP and intracellular calcium 2
• Beta-blockers reduce contractility by blocking sympathetic effects
• Calcium channel blockers reduce calcium influx and contractility

Integration of Control Mechanisms

The regulation of heart muscle contraction involves complex interactions between:

1. Central nervous system (brain centers controlling autonomic outflow)
2. Autonomic nervous system (sympathetic and parasympathetic)
3. Intrinsic cardiac nervous system (local neural networks)
4. Cellular mechanisms (calcium handling, contractile proteins)
5. Metabolic factors (oxygen, substrates, waste products)

This multilevel control system ensures that cardiac output can be precisely adjusted to meet the body's changing demands under various physiological and pathological conditions.