Electrophysiology and Heart Rate Regulation

Key Topics

• Intrinsic vs Extrinsic Innervation
• Sympathetic and Parasympathetic Nervous System Roles
• Beta-1 Adrenergic Receptors
• Action Potentials and Heart Rate

Intrinsic vs Extrinsic Innervation

• Intrinsic Innervation: Sets normal sinus rhythm.
• Extrinsic Innervation: Adjusts heart rate above or below sinus rhythm.

Nervous System Effects on Heart Rate

• Sympathetic Nervous System:
  • Increases heart rate and contractility.
  • Mechanism:
    • Release of norepinephrine and epinephrine.
    • Binds to Beta-1 adrenergic receptors.
    • Activates G stimulatory protein, leading to the conversion of ATP to cyclic AMP.
    • Protein kinase A phosphorylates L-type calcium channels, increasing calcium entry, depolarization, and heart rate.
• Parasympathetic Nervous System:
  • Decreases heart rate.
  • Mechanism:
    • Release of acetylcholine via vagus nerve.
    • Binds to muscarinic type 2 receptors.
    • Activates G inhibitory proteins, leading to hyperpolarization of the cell.
    • Slows down action potential generation.

The mechanism of heart rate regulation is complex, involving both intrinsic and extrinsic factors. Here's a breakdown of how the sympathetic and parasympathetic nervous systems work:

Sympathetic Nervous System (Increases Heart Rate and Contractility)

1. Norepinephrine and Epinephrine Release: Sympathetic neurons release norepinephrine, and the adrenal medulla releases epinephrine. Both these neurotransmitters bind to beta-1 adrenergic receptors located on the heart's nodal and contractile cells.

2. Signal Transduction: The binding triggers a signaling cascade. Beta-1 receptors are G protein-coupled receptors. The activation of these receptors leads to the activation of a G stimulatory protein. This protein causes the conversion of ATP into cyclic AMP (cAMP).

3. Protein Kinase A Activation: cAMP activates protein kinase A (PKA).

4. Calcium Channel Phosphorylation: PKA phosphorylates L-type calcium channels, increasing their permeability to calcium ions.

5. Calcium Influx: This increased permeability allows more calcium to flow into the cell from the extracellular fluid.

6. Depolarization and Increased Heart Rate: This increased intracellular calcium accelerates depolarization, leading to more frequent action potentials and a faster heart rate.

Parasympathetic Nervous System (Decreases Heart Rate)

1. Acetylcholine Release: Parasympathetic neurons, primarily from the vagus nerve, release acetylcholine. Acetylcholine binds to muscarinic type 2 (M2) receptors on the heart's nodal cells.

2. G Protein Inhibition: M2 receptors are also G protein-coupled receptors, but in this case, they activate a G inhibitory protein.

3. Hyperpolarization: This inhibitory protein leads to the opening of potassium channels, causing potassium ions to leave the cell. This loss of positive charges results in hyperpolarization of the cell membrane.

4. Slower Depolarization and Decreased Heart Rate: Hyperpolarization makes it more difficult for the cell to reach the threshold for depolarization. This slows down the rate of action potential generation, leading to a slower heart rate.

Remember: The sympathetic and parasympathetic systems constantly interact to fine-tune heart rate and contractility, ensuring the cardiovascular system adapts to varying demands.

Heart Rate Conditions

• Tachycardia: Heart rate greater than 100 bpm due to increased depolarization by sympathetic stimulation.
• Bradycardia: Heart rate less than 60 bpm due to hyperpolarization by parasympathetic stimulation.

Positive and Negative Chronotropic Effects

• Positive Chronotropic (Sympathetic): Increases heart rate.
• Negative Chronotropic (Parasympathetic): Decreases heart rate.

Contractility and Blood Pressure

• Sympathetic Influence:
  • Increases contractility and stroke volume.
  • Increases cardiac output and blood pressure.
  • Mechanism: Increased crossbridge formation due to calcium influx.
• Parasympathetic Influence:
  • Reduces heart rate, cardiac output, and blood pressure.

Graphical Representation of Heart Rate

• Sympathetic: More frequent action potentials.
• Parasympathetic: Slower action potentials.

Refractory Periods in Cardiac Muscle

• Absolute Refractory Period: Time where new action potentials can't be initiated.
• Relative Refractory Period: Possible to initiate action potentials with strong stimuli, but risky.

Conclusion

• Importance of nervous system in regulating heart rate and contractility.
• Balance between sympathetic and parasympathetic systems to maintain cardiovascular health.