Why is  Na⁺-K⁺ ATPase electrogenic?

Resting permeability 

At rest: Passive K efflux occurs

-small amount but leaves behind negative charges

-inside of cell memb

1) they have “slow calcium channels” in their cell membrane 

2) they have Ca-ATPase pumps (carriers) in their cell membrane that remove Ca

3) their specialized  endoplasmic reticulum (Sarcoplasmic Reticulum = SR) also have Ca ATPase pumps in their membrane which pumps Ca into the S so that the SR serves as a calcium storage site.

Result:

At rest:   Cytosolic Ca very low (0.05 mmol/L) – this is like other cells

  Extracellular Ca high throughout body (5 mmol/L)

  Sarcoplasmic Reticulum (SR) Ca exceedingly high (> 10 mmol/L)

  Inside surface of cell membrane is negatively charged

Transmembrane Potential in ventricular contractile cell at rest: 

-90 mV

  (inside of cell membrane is more negative than outside)

1. Electrogenic nature of Na-K ATPAse

2. Passive K Efflux

3. Active Ca Removal

1. Fast sodium channel
2. Slow calcium channel
3. Potassium channel

open rapidly (“fast”) in response to loss of transmembrane polarity (“depolarization to threshold”)

Slowly close on their own (200 msec or 0.2 sec)

Contractile (ventricular and atrial)

Excitatory (myoconductive cells...[nodes and networks])

                                •Phase 4 (resting potential) is unstable

Label this HCN Hyperpolarization Cyclic Nucleotide sensitive channels diagram.

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Label A and B

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A: Contractile Cell action potential

B: Excitatory/Conductive Cell action potential

Autonomic Nervous System

Sym: stim β1→increases cAMP→opens HCN →?

Parasym: stim Ach R→opens K channels→?

Physical connection between cells (important during contraction)

1. cell 1 reaches threshold (excitatory/conductive cells do this spontaneously)

     -Fast Na and Slow Ca channels open

2. Sodium and Calcium diffuse thru the connexons, depositing + charges on the

   inside of the cell membrane of cell 2 (causing it to depolarize to threshold)

3. Once cell 2 reaches threshold, N and Ca enter thru fast and slow channels, respectively.

    

   Depolarization can then be transmitted to Cell 3.

    

   Remember that cell 1 has intercalated disc connections

   with many more cells (not just cell 2).

Phase 0: depolarization due to rapid influx of sodium thru "fast" Na+ channels; open only    0.0002 secs

   Phase 1: rapid, short-term fall in cell membrane potential, due to increased Cl- permeability which rapidly declines

   Phase 2: plateau due to Ca++ influx (thru "slow" calcium channels; open for approximately 0.1to 0.2 secs, balancing potassium efflux

   Phase 3: rapid repolarization due to K+ efflux that is not balanced by Ca++ influx

            Phase 4: return to baseline. Phase 4 of all cardiac cell's action potential is unstable, that is, there is spontaneous depolarization due to "spontaneously-opening" Na⁺ channels.There are few of these channels in contractile

            cells of the heart.  (This instability of phase 4 is distinct from skeletal muscle and neuron).

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What is the    Normal resting potential of myocardial cells

The lumina of the heart are lined by endothelial cell referred to as endocardial cells or endocardium.  The intermediate layer (most of the mass) is cardiac muscle.  The outer connective tissue lining is referred to as the epicardium.

The heart muscle is composed of 2 general types of cells, classified on the basis of function as_______ or _________.  

contractile

excitatory/conductive

excitatory

little or no contractile

depolarization

This specialized conduction system is composed of 2 nodes (collections of specialized conductive cells) and a network of cells with long processes. Label the SA node, AV node, AV bundle (bundle of His), Purkinje's libers, Left/right bundle branches

The excitatory/conductive system of the heart is organized into:

collections of cells (nodes)

pathways

Purkinje fibers

SA node for pacemaking

  a. collections of cells (nodes): 

referred to as the sinoatrial or SA node (pacemaker) and atrioventricular or AV node (single path to ventricles, one-way conduction, AV delay, long refractory period). 

  b. pathways: 

4 intra-atrial pathways between the SA and rest of atrium and AV node  (Anterior, Middle, and Posterior Interatrial Tract and Left Atrial Tract); the common bundle (bundle of HIS) connecting the AV node with the ventricles, and the left and right bundle branches which conduct the impulse to the Purkinje fibers

c. Purkinje fibers: 

system of excitatory fibers which conduct the depolarization wave throughout the ventricular myocardium.  Most rapid conduction of action potential.  Two main types of Purkinje systems in domesticated animals: Type A (human, dog, cat) in which the Purkinje fibers are subendocardial or Type B (horse, cow, pig) in which the Purkinje fibers are more elaborate and penetrate deeply into the myocardium.

[image]These diagrams depict electrical activity of the subset of cardiac cells referred to as excitatory or conductive cells (distinguished from the cardiac contractile cells).

These cells do not have Voltage Gated Fast Na Channels but have a different type of Na⁺ channel, referred to as Pacemaker Channels or HCN Channels.  At the beginning of phase 4, in response to hyperpolarization, these  channels spontaneously begin to open.  They are  primarily permeable to Na (some K permeability also occurs), with Na influx causing spontaneous rise in transmembrane potential.  Spontaneously falling permeability of the cell membrane to K⁺ (closure of voltage gated K channels) also contributes to the rise to threshold during phase 4.  This marked instability of phase 4 is referred to as a pacemaker potential.  Once threshold is reached, calcium channels open (as in other cardiac cells) and the result is a slow depolarization caused by calcium influx in the absence of sodium entry thru fast channels.  Repolarization is due to K efflux after closure of the ca channels, as in other cardiac cells.

All cardiac excitatory/conductive cells have a tendency to spontaneously depolarize but SA nodal cells do it more rapidly, reaching threshold first normally.

What is a synctium

A syncytium is a mass or lattice of cells acting in unison, like a multinucleate mass.  Intercalated discs between adjacent cardiac muscle cells tie them together mechanically and electrically. 

The intercalated disc is composed of 3 structures:  two mechanical ones: intermediate junctions which connect adjacent myofibrils and desmosomes which connect cellular cytoskeleton to the intermediate junction, and an electrical structure, gap junction, which links adjacent myofibrils electrically by allowing intercellular ionic transmission. 

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Cell to cell transmission of the action potential occurs across the gap junctions (connexons) within the intercalated discs. This spreading of excitation through sequential "transmission" of the depolarization process from cell to cell is sometimes referred to as the cardiac impulse.  The 2 atria are electrically interconnected as are the 2 ventricles.  The atria are separated from the ventricles by an insulating fibrous band. Thus the heart behaves electrically as 2 lattice-like syncytia (the ventricular syncytium and the atrial syncytium). 

All-or-Nothing Principle:

Allows the entire atria of the dog and horse to depolarize within 0.04 seconds and the entire ventricle to depolarize within 0.06 seconds. 

Hierarchy of the rate of spontaneous phase 4 depolarization:

The heart rate can be modified by the autonomic nervous system (REVIEW THIS MATERIAL) which innervates the SA node, AV node (the ventricular contractile cells are also innervated but this innervation generally affects strength of contraction only). The rate of spontaneous depolarization of SA nodal cells  (“pacemaker potential”) is controlled by the autonomic nervous system.   Parasympathetic stimulation (=binding of acetylcholine to muscarinic receptors) slows the rate of spontaneous depolarization, thereby slowing heart rate.  Sympathetic stimulation (=binding of norepinephrine or epinephrine to ß1 receptors) increases heart rate.  In particular, the neurotransmitters of the ANS alter the phase 4 permeability of the pacemaker cells, thereby increasing or decreasing the rate of the SA nodal spontaneous depolarization.

Which of the following EKG devices will record a positive value? (Could be more than one answer)

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