Cardiac Physiology: Electrophysiology & Excitation

Electrophysiology

electrical activity that occurs in the heart

The mechanical activity (squeezing of the heart) is caused by...

changes in cardiac cell membrane polarity and the movement of ions

Cardiac cells are __________

polarized

polarization

the concentration of ions is different inside the cell and outside the cell

Transmembrane potential

The electrical potential difference (voltage) across a cell's plasma membrane

What is the resting potential of most cardiac muscle cells?

-80 to -90 mV

depolarization

an increase in the membrane potential caused by an influx of positive ions

Depolarization is mainly due to...

influx of sodium

repolarization

Return of the cell to resting polarized state

Repolarization is mainly due to...

exit of potassium

an action potential occurs when...

there is a reversal of the charge inside the cell from negative to positive

Three types of cardiac cells:

1.) cardiomyocytes

2.) Purkinje cells

3.) pacemaker cells

cardiomyocytes

contractile cells of the atrium and ventricle

Where are cardiomyocytes found?

myocardium (walls of atria and ventricles)

Purkinje cells

conduction cells of the heart that transmit electrical signals

Where are Purkinje cells found?

within the heart's conduction system

pacemaker cells

noncontractile cells that spontaneously depolarize to keep the heart beating

where are pacemaker cells found?

SA and AV nodes

The action potential of what cell type is responsible for initiating the cardiac cycle?

pacemaker cells

The action potential of what cell type is responsible for conduction within the heart?

cardiomyocytes

What cell types use Na channels for depolarization?

cardiomyocytes and Purkinje cells

What cell types use the slow Ca current for depolarization?

pacemaker cells

Switch terms and definitions

Switch terms and definitions

cardiomyocytes and Purkinje cells

This is the action potential graph for what cell types?

pacemaker cells

This is the action potential graph for what cell types?

Switch terms and definitions back

Switch terms and definitions back

Five phases of the action potential in cardiac cells:

1.) phase 0

2.) phase 1

3.) phase 2

4.) phase 3

5.) phase 4

phase 0

depolarization

phase 1

brief, early repolarization

phase 2

plateau phase

phase 3

repolarization

phase 4

return to resting membrane potential

Pacemaker cells do not have a phase _____ or ____during their action potential

1 or 2 (brief repolarization and plateau)

Main ion channel that determines the resting membrane potential

sodium potassium ATPase pump

The Na/K ATPase pump moves _______ sodium ______ the cell and _______ potassium _______ the cell

3; out of

2; into

The Na/K ATPase pump creates a ________ charge inside the cell

negative

*the resting membrane potential

There is typically high concentrations of potassium __________ the cell and high concentrations of sodium _________ the cell

inside

outside

What takes place during phase 0 of the action potential (cardiomyocytes and purkinje cells)

Na channels open and allow Na to rush into the cell --> depolarization!

What is the stimulus that causes Na channels to open?

voltage change OR ligand binding to a receptor

What takes place during phase 1 of the action potential (cardiomyocytes and purkinje cells)

K channels open and K rushes out of the cell --> brief repolarization

What takes place during phase 2 of the action potential (cardiomyocytes and purkinje cells)

Ca channels open and Ca rushes into the cell --> plateau

Why does a plateau occur during phase 2?

result of K ions leaving the cell during phase 1 (brief repolarization) and Ca ions entering the during phase 2

What is the role of Ca entering the cell?

it will help trigger a cascade of events that promote more calcium to enter the cell and ultimately stimulate myocardial contraction

What takes place during phase 3 of the action potential (cardiomyocytes and purkinje cells)

K channels open and K rushes out of the cell --> repolarization

What takes place during phase 4 of the action potential (cardiomyocytes and purkinje cells)

Na/K pump returns cell to resting membrane potential

What takes place during phase 0 of the action potential (pacemaker cells)

calcium channels open and allow calcium in --> depolarization

What takes place during phase 3 of the action potential (pacemaker cells)

K channels open and K rushes out of the cell --> repolarization

What takes place during phase 4 of the action potential (pacemaker cells)

the cell reaches its resting membrane potential through the "funny current"

funny current

spontaneous automatic drift towards the resting membrane potential due to slow influx of Na AND K

The funny current causes the membrane potential to become more _________

positive

*towards resting membrane potential

Once the funny current causes the cell to reach its membrane potential, what happens?

Ca channels open, triggering phase 0 depolarization

The resting membrane potential of cardiomyocytes and purkinje cells is ____ mV

The resting membrane potential of pacemaker cells is ____ mV

-80 to -90 mV

-50 mV

What causes depolarization in cardiomyocytes/purkinje cells?

Pacemaker cells?

fast inward sodium current

slow inward calcium current

For each cell, when the resting membrane potential is reached, this triggers...

depolarization to occur

conductance

the ease with which ions flow through a channel and in what direction; aka permeability

Membrane conductance ________ throughout an action potential

varies

Four things that cause the opening of an ion channel:

1.) voltage changes

2.) time duration

3.) concentration gradients

4.) ligand binding

Three ligands that open channels in the heart:

1.) norepinephrine

2.) epinephrine

3.) acetylcholine

Norepinephrine and epinephrine are released by...

sympathetic nerves and adrenal glands

Norepinephrine and epinephrine bind to...

beta-adrenergic receptors

beta-adrenergic receptors

cause an increase in the force of contraction of the heart, an increased heart rate, and bronchial dilation

acetylcholine is released by...

the vagus nerve

acetylcholine binds to...

muscarinic receptors (M2)

muscarinic receptors

modulate channel conductance; decrease the force of contraction in the heart and lower heart rate

In resting cardiomyocytes, the cell membrane has high conductance to ________ and low conductance to _______ and ___________

potassium; sodium and calcium

Because the resting membrane of cardiomyocytes is highly permeable to potassium...

this ion is constantly drifting out of the cell along its concentration gradient (remember potassium is high within the cell and low outside of the cell)

Because the resting membrane of cardiomyocytes has low permeability to sodium...

little sodium crosses the membrane, despite an enormous concentration gradient for entry

Channelopathies

diseases and disorders that are the result of ion channel dysfunction; can cause arrhythmias

Anti-arrhythmic drugs

block ion channels to help treat arrhythmias

Example of anti-arrhythmic drug

lidocaine --> Na channel blocker

ionophores

lipid soluble chemicals that act as a carrier of ions across the cell membrane; sometimes added to animal feeder as growth promoters

Problem with ionophores

when ingested in excessive amounts by cattle or when fed to unintended species (especially horses and camelids), the compound can be highly toxic to the heart causing arrhythmias, heart failure, and even death

Three main ion channels in the heart:

1.) Na channels

2.) Ca channels

3.) K channels

Na channels are found in what cardiac cell type?

cardiomyocytes and Purkinje cells

Role of Na channels

fast sodium influx that depolarizes the cell during phase 0

What causes activation of Na channels?

when transmembrane voltage increases to -60 to -70 due to spontaneous depolarization of pacemaker cells in the SA node

The slope of phase 0 determines the conduction _________ from cell-to-cell

velocity

The Na channel is both ________ gated and _________ dependent

voltage gated and time dependent (shuts down milliseconds after opening)

Na channels are aka...

fast channels since they open and close so quickly

Ca channels are found in what cardiac cell type?

all cardiac cells

Ca is required for __________ of muscle cells

contraction

Two functions of Ca channels in pacemaker cells:

2.) important for depolarization in pacemaker cells

3.) contributes to the spontaneous pacemaker currents of SA node cells

Functions of Ca channels in cardiomyocytes:

responsible for the plateau phase of the action potential, resulting in calcium influx into the cell

Calcium influx into the cardiomyocyte is important for...

calcium-induced calcium release within the cell that helps lead to myocardial contraction

Two types of Ca channels based on activation

1.) voltage gated

2.) ligand gated

Two types of Ca voltage gated channels in the heart:

1.) T-type

2.) L-type

T-type Ca channels

open at low voltages and allow for short bursts of Ca entry

Where are T-type Ca channels found?

pacemaker cells (SA node)

*help initiate muscle contraction in late phase 4!!

L-type Ca channels

open at high voltages and allow for sustained Ca entry

Where are L-type Ca channels found?

cardiomyocytes (cause plateau phase) and pacemaker cells (slow depolarization)

Two types of Ca ligand gated channels in the heart:

1.) norepinephrine gated

2.) epinephrine gated

Norepinephrine and epinephrine bind to...

beta-receptors

What happens when Norepinephrine and epinephrine bind to beta-receptors?

causes Ca influx, which leads towards greater heart contraction and faster heart beat

K channels are found in what cardiac cell type?

all cardiac cells

Three functions of K in cardiomyocytes:

1.) phase 1 brief repolarization

2.) phase 2 plateau (as Ca enters, K leaves, creating plateau)

3.) phase 3 repolarization

Two functions of K in pacemaker cells

1.) phase 3 repolarization

2.) facilitates funny current

Repolarization is mainly due to _____ channels letting this ion go ______ of the cell

K; out of

K channels determine the ________ of repolarization

speed

effective refractory period

phase in which cells are incapable of depolarizing (occurs during repolarization)

A faster repolarization will _________ the effective refractory period

decrease