Electrophysiology of Heart

Electrophysiology of the Heart

Subject: Pharmacotherapeutics-I | Course: Doctor of Pharmacy (Pharm.D) | Topic: Electrophysiology of the Heart

1. Introduction

Cardiac electrophysiology is the study of the electrical activity of the heart, including how electrical impulses are generated and conducted to produce a normal heartbeat.

The heart generates its own impulses without stimulation from the brain. This property is called automaticity. Specialised cardiac cells produce the impulses, and the cardiac conduction system carries them to the myocardium, which then contracts and pumps blood.

Key points

•        The heart can initiate impulses independently of the nervous system.

•        The SA node is the natural pacemaker.

•        Electrical impulses control the rate and rhythm of the heartbeat.

•        The autonomic nervous system modifies heart rate and force of contraction but does not normally initiate each beat.

2. Automaticity

Definition: Automaticity is the intrinsic ability of specialised cardiac cells to generate electrical impulses spontaneously, without external stimulation.

•        It is an intrinsic property of pacemaker cells.

•        It allows the heart to beat independently of the nervous system.

•        The SA node normally fires at about 60–100 impulses per minute (the intrinsic rate is nearer 100/min; vagal tone slows the resting rate).

•        Latent pacemakers take over if the SA node fails: AV node about 40–60/min, Purkinje fibres about 20–40/min.

Clinical importance: Abnormal automaticity can cause cardiac arrhythmias.

3. Types of Cardiac Muscle Cells

The myocardium contains two major cell types.

A. Nodal (pacemaker) cells

•        Depolarise spontaneously.

•        Generate very little contractile force.

•        Have an unstable resting membrane potential.

•        Found mainly in the SA node and AV node.

Function: Generation and regulation of electrical impulses.

B. Contractile cells (working myocardium)

•        Form the bulk of the atrial and ventricular walls.

•        Contain contractile proteins (actin, myosin).

•        Have a stable resting membrane potential (about –90 mV).

•        Contract when stimulated by an impulse.

Function: Generating the mechanical force that pumps blood into the pulmonary artery and aorta.

4. Cardiac Conduction System

The conduction system is a network of specialised cells that generate and conduct impulses through the heart.

Pathway: SA node → atrial muscle (internodal pathways) → AV node → Bundle of His → right and left bundle branches → Purkinje fibres → ventricular muscle.

conduction pathway · 7 steps

The AV node holds the impulse for about 0.1 s so the ventricles can fill before they contract.

Component	Location and features	Function
SA node	Upper right atrium, near the opening of the superior vena cava; fires about 60–100/min	Natural pacemaker; initiates each heartbeat
Atrial conduction	Spread of the impulse through right and left atria	Atrial contraction; fills the ventricles
AV node	Lower right atrium, in the interatrial septum near the opening of the coronary sinus	Delays the impulse by about 0.1 s so the ventricles fill before they contract
Bundle of His	Passes from the AV node into the interventricular septum	Conducts impulses to the ventricles; divides into two branches
Right and left bundle branches	Run along the interventricular septum	Carry impulses to the right and left ventricles
Purkinje fibres	Subendocardial network in the ventricular walls	Rapid, coordinated ventricular depolarisation and contraction

5. Cellular Electrophysiology

Electrical activity arises from the movement of ions across the cell membrane.

•        Sodium (Na⁺): rapid depolarisation in contractile cells.

•        Potassium (K⁺): mainly repolarisation.

•        Calcium (Ca²⁺): depolarisation in nodal cells, and the trigger for contraction.

There are two types of cardiac action potential: the nodal (pacemaker) action potential and the contractile cell action potential.

6. Nodal Cell Action Potential (SA Node)

Nodal cells have no stable resting potential. The SA nodal action potential has three phases: 4, 0 and 3 (phases 1 and 2 are absent).

Phase 4 – Pacemaker potential (slow diastolic depolarisation)

•        Begins right after repolarisation, at the maximum diastolic potential (about –60 mV).

•        The funny current (I_f, through HCN channels) allows a slow inward flow of mainly Na⁺.

•        Outward K⁺ current decreases.

•        T-type Ca²⁺ channels open late in the phase and add to the depolarisation.

•        The membrane potential drifts upward until it reaches the threshold (about –40 mV).

Phase 0 – Depolarisation

•        At threshold, L-type Ca²⁺ channels open and Ca²⁺ enters the cell.

•        Result: a relatively slow upstroke.

Remember: In nodal cells phase 0 is caused by calcium; in ventricular contractile cells it is caused by sodium.

Phase 3 – Repolarisation

•        Ca²⁺ channels close.

•        K⁺ channels open and K⁺ leaves the cell.

•        The membrane potential returns to the maximum diastolic potential and the next pacemaker cycle begins.

7. Contractile Cell Action Potential (Ventricular Muscle)

Contractile cells have a stable resting potential of about –90 mV and a five-phase action potential (0, 1, 2, 3, 4).

Phase	Name	Ion movement	Result
4	Resting	High K⁺ permeability (inward rectifier K⁺ current)	Stable potential of about –90 mV
0	Rapid depolarisation	Fast Na⁺ channels open; Na⁺ rushes in	Inside becomes positive
1	Initial repolarisation	Na⁺ channels inactivate; transient outward K⁺ current	Small, brief fall in potential
2	Plateau	Ca²⁺ influx (L-type) balances K⁺ efflux	Potential stays near constant
3	Rapid repolarisation	Ca²⁺ channels close; K⁺ efflux increases	Returns to about –90 mV

Importance of the plateau (phase 2)

•        Ca²⁺ enters and triggers contraction.

•        It prolongs the action potential.

•        It produces a long refractory period, which prevents sustained contraction (tetany).

Comparison: nodal vs contractile cells

Feature	Nodal cells	Contractile cells
Main function	Generate impulses	Produce contraction
Resting potential	Unstable	Stable (about –90 mV)
Phase 0	Ca²⁺ influx	Na⁺ influx
Phase 1	Absent	Present
Phase 2	Absent	Present
Phase 3	K⁺ efflux	K⁺ efflux
Phase 4	Pacemaker potential	Resting phase

action potentials · nodal vs contractile

Nodal cells reach threshold by slow drift and use Ca²⁺ for phase 0. Contractile cells start from a stable –90 mV, use Na⁺ for phase 0 and hold a Ca²⁺ plateau in phase 2.

8. Mechanism of Cardiac Muscle Contraction

Cardiac contraction occurs through excitation–contraction coupling: the process by which an electrical impulse produces mechanical contraction.

1.      Calcium entry: During phase 2, L-type Ca²⁺ channels open and Ca²⁺ enters from the extracellular fluid.

2.      Calcium-induced calcium release (CICR): Entering Ca²⁺ activates ryanodine receptors (RyR2) on the sarcoplasmic reticulum, which releases much more Ca²⁺ into the sarcoplasm.

3.      Binding to troponin C: Ca²⁺ binds troponin C, changing the shape of the troponin complex. Tropomyosin moves off the myosin-binding sites on actin.

4.      Cross-bridge formation: Myosin heads attach to actin.

5.      Power stroke: Myosin heads pull actin towards the centre of the sarcomere. The sarcomere shortens and the muscle contracts.

9. Intercalated Discs and Functional Syncytium

Cardiac muscle cells are joined end-to-end by intercalated discs, which give both mechanical and electrical connection.

Gap junctions

•        Channels formed by connexin proteins (mainly connexin 43).

•        Allow ions and small molecules to pass between neighbouring cells.

•        Let impulses spread rapidly, so cells contract in a coordinated way.

•        Function: electrical communication.

Desmosomes (and fascia adherens)

•        Provide strong mechanical attachment between cells.

•        Prevent cells from pulling apart during repeated contraction.

•        Function: mechanical attachment.

Functional syncytium: A group of individual cells that behave as a single unit because they are electrically connected through gap junctions. The heart has two syncytia:

•        Atrial syncytium: both atria contract together.

•        Ventricular syncytium: both ventricles contract together.

The fibrous skeleton of the heart electrically insulates the atria from the ventricles. Under normal conditions the AV node and His bundle are the only electrical connection between them.

10. Mechanism of Cardiac Muscle Relaxation

Relaxation (diastole) requires Ca²⁺ to be removed from the sarcoplasm.

1.      Ca²⁺ channels close: L-type channels close, so no more Ca²⁺ enters.

2.      Reuptake into the sarcoplasmic reticulum: SERCA (sarco/endoplasmic reticulum Ca²⁺-ATPase) pumps Ca²⁺ back into the SR using ATP. This is the main route of removal.

3.      Extrusion from the cell:

o        Na⁺/Ca²⁺ exchanger (NCX): brings in 3 Na⁺ and removes 1 Ca²⁺. It is driven by the Na⁺ gradient, not directly by ATP.

o        Plasma membrane Ca²⁺-ATPase (PMCA): uses ATP to pump Ca²⁺ out of the cell.

4.      Ca²⁺ detaches from troponin C: Tropomyosin covers the binding sites on actin again, and cross-bridges release.

Result: The muscle relaxes and the chambers refill with blood.

11. Role of ATP

•        Myosin detachment: ATP binds myosin and releases it from actin.

•        Myosin activation: ATP hydrolysis provides the energy for the power stroke.

•        Calcium reuptake: SERCA needs ATP.

•        Calcium extrusion: PMCA needs ATP.

•        Ionic balance: The Na⁺/K⁺-ATPase pumps 3 Na⁺ out and 2 K⁺ in per ATP, maintaining the gradients needed for electrical activity. It also keeps the Na⁺ gradient that drives NCX.

12. Important Ions – Summary

Ion	Role
Sodium (Na⁺)	Rapid depolarisation in contractile cells (phase 0); contributes to the pacemaker current I_f
Potassium (K⁺)	Repolarisation; sets the resting potential
Calcium (Ca²⁺)	Nodal depolarisation (phase 0), plateau in contractile cells, and muscle contraction

13. Clinical and Pharmacological Importance

Abnormal impulse generation or conduction causes arrhythmias. Many cardiovascular drugs act by changing ion movement across cardiac cell membranes.

Drug	Class / target	Effect
Verapamil	Non-dihydropyridine Ca²⁺ channel blocker (blocks L-type channels)	Slows SA firing and AV nodal conduction
Diltiazem	Non-dihydropyridine Ca²⁺ channel blocker	Reduces Ca²⁺ entry; slows AV nodal conduction
Metoprolol	Selective β1-blocker	Decreases SA nodal firing rate and slows AV nodal conduction
Adenosine	Activates A1 receptors, increasing K⁺ efflux and hyperpolarising nodal cells	Transient AV nodal block; used to terminate certain supraventricular tachycardias
Amiodarone	Class III (mainly K⁺ channel blocker); also blocks Na⁺ and Ca²⁺ channels and has β-blocking action	Prolongs action potential duration and refractory period
Lidocaine	Class IB (Na⁺ channel blocker)	Acts mainly on ventricular tissue; used in ventricular arrhythmias

Clinical importance: Understanding cardiac electrophysiology explains how antiarrhythmic drugs work and how they are used.

14. Summary of Important Points

Topic	Key point
Cardiac electrophysiology	Study of the electrical activity of the heart
Automaticity	Spontaneous impulse generation
SA node	Natural pacemaker
AV node	Brief conduction delay (about 0.1 s)
Bundle of His	Conducts impulses towards the ventricles
Purkinje fibres	Rapid ventricular conduction
Nodal phase 0	Ca²⁺ influx
Contractile phase 0	Na⁺ influx
Phase 2	Plateau phase
Troponin C	Binds Ca²⁺
SERCA	Pumps Ca²⁺ into the sarcoplasmic reticulum
NCX	Exchanges 3 Na⁺ for 1 Ca²⁺
Gap junctions	Electrical communication
Desmosomes	Mechanical attachment
ATP	Energy for contraction and relaxation