Cardiovascular | Electrophysiology | Extrinsic Cardiac Conduction System

Introduction to Electrophysiology and Extrinsic Innervation

In this section, the video introduces the topic of electrophysiology and focuses on extrinsic innervation of the heart. It discusses how the sympathetic and parasympathetic nervous systems affect heart rate and contractility.

Sympathetic Nervous System and Heart Rate Regulation

• The sympathetic nervous system releases chemicals like norepinephrine and epinephrine.

• These chemicals bind to beta-1 adrenergic receptors located on the heart.

• Activation of these receptors stimulates intracellular processes, including activation of a G stimulatory protein.

• The G stimulatory protein activates an effector enzyme called adenylate cyclase.

• Adenylate cyclase converts ATP into cyclic AMP (cAMP).

• cAMP can activate protein kinase A (PKA), which targets L-type calcium channels on the cell membrane.

• PKA phosphorylates these channels, leading to increased calcium influx into the cell.

• Increased calcium influx results in more frequent depolarization and action potentials, leading to an increased heart rate (tachycardia).

Parasympathetic Nervous System and Heart Rate Regulation

• The parasympathetic nervous system releases acetylcholine.

• Acetylcholine slows down heart rate by inhibiting the activity of adenylate cyclase.

• This reduces cAMP levels and decreases calcium influx into the cell.

• Decreased calcium influx leads to slower depolarization and fewer action potentials, resulting in a decreased heart rate.

Pathway of Nerves in Blood Pressure Regulation

This section briefly mentions that nerves involved in blood pressure regulation come from either the spinal cord or brain stem. However, it does not go into detail about the pathway.

Sympathetic and Parasympathetic Nervous System Effects on Heart Rate and Contractility

This section explains how the sympathetic and parasympathetic nervous systems affect heart rate and contractility differently.

Sympathetic Nervous System and Contractility

• The sympathetic nervous system affects the contractility of the heart.

• Activation of beta-1 adrenergic receptors by norepinephrine and epinephrine leads to increased calcium influx into the cell.

• Increased calcium levels enhance contractile force, resulting in increased contractility of the heart.

Parasympathetic Nervous System and Contractility

• The parasympathetic nervous system does not have a significant effect on contractility.

• Its main role is to regulate heart rate rather than contractile force.

Mechanism of Adenylate Cyclase Activation

This section explains how adenylate cyclase is activated by G stimulatory protein, leading to cyclic AMP production.

• G stimulatory protein activates adenylate cyclase by binding GTP instead of GDP.

• Activated adenylate cyclase converts ATP into cyclic AMP (cAMP).

• cAMP can then activate protein kinase A (PKA), which plays a role in regulating heart rate and contractility.

Protein Kinase A and Calcium Channels

This section discusses how protein kinase A (PKA) phosphorylates L-type calcium channels, leading to increased calcium influx into the cell.

• PKA phosphorylates L-type calcium channels located on the cell membrane.

• Phosphorylation of these channels stimulates their opening, allowing more calcium to enter the cell.

• Increased calcium influx enhances depolarization and action potential generation, resulting in increased heart rate.

Increased Calcium Influx and Depolarization

This section explains how increased calcium influx due to sympathetic activation leads to quicker depolarization and increased heart rate.

• Sympathetic activation increases calcium influx into the cell.

• The increased calcium levels result in more frequent depolarization of the cell.

• Quicker depolarization leads to more action potentials being generated, which increases the heart rate (tachycardia).

Slowing Down Heart Rate with Parasympathetic Nervous System

This section discusses how the parasympathetic nervous system slows down heart rate by inhibiting adenylate cyclase activity.

• The parasympathetic nervous system releases acetylcholine.

• Acetylcholine inhibits adenylate cyclase activity, reducing cyclic AMP (cAMP) production.

• Decreased cAMP levels lead to decreased calcium influx into the cell.

• Reduced calcium influx results in slower depolarization and fewer action potentials, leading to a decreased heart rate.

New Section

This section explains the activation of the type 2 receptor and its effect on heart rate through the parasympathetic nervous system.

Activation of Type 2 Receptor

• Acetylcholine binds to the type 2 receptor, activating a G inhibitory protein.

• The G inhibitory protein consists of alpha, beta, and gamma inhibitory components.

• Acetylcholine binding causes the alpha inhibitory component to separate from beta and gamma inhibitory components.

• Beta and gamma inhibitory components bind to special channels in the cell membrane that are sensitive to potassium movement.

Effect on Heart Rate

• Binding of beta and gamma inhibitory subunits to potassium channels causes them to open.

• Potassium starts flowing out of the cell, leading to a loss of positive ions inside the cell.

• The cell becomes more negative, resulting in decreased depolarization and action potentials.

• Decreased action potential frequency leads to a decrease in heart rate (bradycardia).

Inhibition of Adenylate Cyclase

• The alpha inhibitory unit binds to adenylate cyclase and inhibits its activity.

• Inhibition of adenylate cyclase decreases cyclic AMP levels and protein kinase A levels.

• Decreased phosphorylation reduces calcium entry into cells, further decreasing action potential frequency and heart rate.

Parasympathetic Nervous System

• The vagus nerve supplies parasympathetic input to nodal cells, contributing to bradycardia.

• Sympathetic nerves come from chain ganglia or cervical ganglion, while epinephrine is released from the adrenal medulla.

Sympathetic Nervous System Effects

• Sympathetic nervous system activation increases heart rate (positive chronotropic action).

• Parasympathetic nervous system activation decreases heart rate (negative chronotropic action).

Receptors on Contractile Cells

• Norepinephrine and epinephrine bind to beta-1 adrenergic receptors on contractile cells.

• This binding can also affect heart rate through the sympathetic nervous system.

New Section

This section discusses the role of the sympathetic and parasympathetic nervous systems in regulating heart rate.

Role of Sympathetic Nervous System

• The sympathetic nervous system aims to increase heart rate (positive chronotropic action).

• Sympathetic nerves come from chain ganglia or cervical ganglion, while epinephrine is released from the adrenal medulla.

Role of Parasympathetic Nervous System

• The parasympathetic nervous system aims to decrease heart rate (negative chronotropic action).

• The vagus nerve supplies parasympathetic input to nodal cells, contributing to bradycardia.

Effect on Heart Rate

• Activation of the sympathetic nervous system increases heart rate.

• Activation of the parasympathetic nervous system decreases heart rate.

New Section

This section explains the role of adenylate cyclase and cyclic GMP in activating protein kinase A, which leads to two critical events: phosphorylation of channels on the sarcoplasmic reticulum and phosphorylation of L-type calcium channels.

Adenylate Cyclase and Protein Kinase A Activation

• Adenylate cyclase converts ATP into cyclic GMP.

• Cyclic GMP activates protein kinase A (PKA).

• Increased levels of PKA have two important effects.

Phosphorylation of Channels on Sarcoplasmic Reticulum

• PKA phosphorylates special channels on the sarcoplasmic reticulum called phospholamban.

• Phosphorylation stimulates these channels, allowing them to open and bring in more calcium ions into the sarcoplasmic reticulum.

• The purpose is to increase the excitable organelle's storage of calcium.

Phosphorylation of L-Type Calcium Channels

• PKA also phosphorylates L-type calcium channels.

• This results in an increased influx of calcium ions into the cell.

• The excess calcium stimulates ryanodine receptors type 2, leading to even more release of calcium from the sarcoplasmic reticulum.

New Section

This section discusses how increased calcium levels affect troponin, tropomyosin, cross bridge formations, and ultimately enhance cardiac contractions and blood pressure.

Increased Calcium Levels and Troponin Interaction

• The increased release of calcium from the sarcoplasmic reticulum leads to more interactions with troponin.

• This interaction causes movement of tropomyosin, allowing for increased actin-myosin interactions.

• Increased cross bridge formations result in more power strokes and sliding of myofilaments.

Effects on Cardiac Contractions and Blood Pressure

• Enhanced cross bridge cycling increases the speed and strength of contractions.

• This, in turn, increases the pumping action of the heart and cardiac output.

• Increased cardiac output leads to an increase in stroke volume and subsequently raises blood pressure.

New Section

This section explains how the sympathetic nervous system affects contractility, heart rate, cardiac output, and blood pressure.

Sympathetic Nervous System and Contractility

• The sympathetic nervous system increases contractility by enhancing cross bridge formations and speeding up contraction speed.

• These effects result from increased protein kinase A activity.

Relationship Between Heart Rate and Blood Pressure

• Increased heart rate directly correlates with increased blood pressure.

• Cardiac output is equal to heart rate multiplied by stroke volume.

• Blood pressure is equal to cardiac output multiplied by total peripheral resistance.

New Section

This section highlights how both the sympathetic and parasympathetic nervous systems can influence nodal cells' activity, contractile cells' activity, heart rate, cardiac output, and blood pressure.

Sympathetic Nervous System Effects

• The sympathetic nervous system increases heart rate through norepinephrine acting on beta-adrenergic receptors.

• Increased heart rate leads to increased cardiac output and subsequently raises blood pressure.

Parasympathetic Nervous System Effects

• The parasympathetic nervous system decreases heart rate through acetylcholine acting on muscarinic receptors.

• Decreased heart rate reduces cardiac output and lowers blood pressure.

Conclusion

The transcript explains how adenylate cyclase activates protein kinase A (PKA), which phosphorylates channels on the sarcoplasmic reticulum (phospholamban) and L-type calcium channels. This leads to increased calcium levels, enhancing troponin interaction and cross bridge formations, resulting in stronger cardiac contractions and increased blood pressure. The sympathetic nervous system increases contractility, heart rate, and blood pressure, while the parasympathetic nervous system decreases heart rate and blood pressure.

New Section

This section discusses the differences in action potentials and heart rate regulation between the sympathetic and parasympathetic nervous systems.

Sympathetic Nervous System

• Repolarization occurs quickly, leading to faster action potentials.

• Depolarization occurs much faster compared to the parasympathetic system.

• The sympathetic nervous system increases the rate of action potentials, resulting in a higher heart rate.

Parasympathetic Nervous System

• Depolarization is slow, taking a longer time to occur.

• The heart rate decreases due to a lower frequency of action potentials caused by the parasympathetic system.

New Section

This section explains the refractory period and its importance in heart function.

Refractory Period

• The plateau phase during phase 2 lasts for about 250 milliseconds.

• The refractory period is divided into three parts: absolute refractory period, relative refractory period, and super normal refractory period (not discussed).

• The refractory period allows the heart to rest for approximately 250 milliseconds before another action potential can occur.

• Stimulating the heart with frequent and powerful stimuli during this resting phase can trigger another action potential, known as the relative refractory period.

• It is crucial to obey the absolute refractory period to avoid complications like tetany.

New Section

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