Ninja Nerd Electrophysiology

Introduction to Electrophysiology

  • Overview of electrophysiology and its relevance to heart function.

  • Reminder of previous discussions on the cardiac conduction system and intrinsic mechanisms.

  • Focus on the extrinsic innervation of the heart and regulation of heart rate.

Sympathetic and Parasympathetic Nervous Systems

General Effects

  • Discuss the role of the sympathetic (SNS) and parasympathetic nervous systems (PNS) in controlling heart rate.

  • SNS increases heart rate and contractility.

  • PNS decreases heart rate.

Mechanisms of Sympathetic Nervous System (SNS)

Beta 1 Adrenergic Receptor

  • Definition: A specific receptor in the heart and the juxtaglomerular (JG) cells of the kidney.

  • Functionality:

    • Sympathetic nerves release norepinephrine (NE) and epinephrine (Epi).

    • These neurotransmitters bind to the beta 1 adrenergic receptor, activating intracellular processes.

Signal Transduction Pathway

  1. Activation of G Protein:

    • Activation of the beta 1 receptor activates a G stimulatory protein (Gs).

    • Gs exchanges GDP for GTP.

  2. Activation of Adenylate Cyclase:

    • Gs activates adenylate cyclase, converting ATP to cyclic AMP (cAMP).

  3. Role of Cyclic AMP:

    • cAMP activates protein kinase A (PKA).

    • Definition: Protein kinase A phosphorylates specific target proteins that facilitate cellular responses.

Mechanism of Increased Calcium Entry

  • PKA phosphorylates L-type calcium channels.

    • More calcium ions enter the cell, increasing intracellular calcium concentration.

  • Consequence of increased calcium:

    • Faster depolarization leading to quicker action potentials and increased heart rate.

    • Termed Tachycardia when heart rate > 100 beats per minute.

Mechanisms of Parasympathetic Nervous System (PNS)

M2 Muscarinic Receptor

  • Definition: Receptor activated by acetylcholine (ACh) released from the vagus nerve.

  • Functionality:

    • Binding of ACh activates a G inhibitory protein (Gi), causing:

    1. Separation of G protein components: Alpha-inhibitory separates from beta and gamma subunits.

    2. Effect of Beta/Gamma Subunits:

      • These subunits open potassium channels, increasing potassium efflux.

Hyperpolarization Effect

  • Increased potassium efflux makes the inside of the cell more negative (hyperpolarization).

  • Outcome of Hyperpolarization:

    • Decreased rate of depolarization and decreased heart rate.

    • Termed Bradycardia when heart rate < 60 beats per minute.

Inhibition of Adenylate Cyclase

  • Alpha-inhibitory also inhibits adenylate cyclase, lowering cAMP levels, which decreases PKA activity:

    • Decreased phosphorylation of calcium channels.

    • Reduced calcium entry into the cell, leading to lower action potential frequency and decreased heart rate.

Summary of Effects on Heart Rate

  • SNS leads to Positive Chronotropic Action:

    • Increases heart rate via increased calcium entry and faster depolarization.

  • PNS leads to Negative Chronotropic Action:

    • Decreases heart rate through hyperpolarization and inhibition of calcium influx.

Sympathetic Nervous System and Contractility

Role of Sympathetic Nervous System on Contractile Cells

  • NE and EPI bind to beta 1 adrenergic receptors on contractile cells.

  • Similar pathway as discussed for the SA node, affecting calcium handling and contractility:

    1. Gs protein activation leads to increased cAMP and PKA activity.

    2. PKA phosphorylates:

    • L-type calcium channels (increase calcium influx).

    • Phospholamban (increases calcium uptake by the sarcoplasmic reticulum).

Consequences of Increased Contractility

  • Higher intracellular calcium leads to more cross-bridge cycling between actin and myosin:

    • Increased contraction strength and speed.

    • Resultant increase in stroke volume and overall cardiac output.

  • Cardiovascular Implications:

    • Higher cardiac output can lead to increased blood pressure.

Cardiac Output Relationships

  • **Formulas:

    • Cardiac Output (CO) = Heart Rate (HR) × Stroke Volume (SV)**

  • Blood Pressure (BP) relationship:

    • BP = CO × Total Peripheral Resistance.

  • Increasing HR or SV due to sympathetic stimulation raises BP.

Graphical Representation of Heart Rate Changes

  • Normal heart rate represented visually alongside sympathetic and parasympathetic stimulation:

    • Sympathetic: Faster depolarization and more frequent action potentials.

    • Parasympathetic: Slower depolarization, leading to fewer action potentials.

Refractory Period in Cardiac Cycles

Definition and Importance

  • Refractory Period: Time during which the heart cannot produce a new action potential; crucial for heart function to prevent tetany.

  • Duration: Approximately 250 milliseconds, includes:

    1. Absolute Refractory Period: No new action potentials can be initiated.

    2. Relative Refractory Period: A stronger than usual stimulus can generate an action potential.

Clinical Implications of Refractory Period

  • Importance of adhering to the refractory period to prevent dangerous arrhythmias such as tetany.

Conclusion

  • Overview of how the autonomic nervous system can finely tune heart function through intricate molecular pathways.

  • The understanding of these mechanisms is critical for tackling cardiovascular issues.