Cardiac Action Potential - myocardial cells

 Phase 0 - the rapid depolarization phase

1.) Depolarizing current makes "fast" NA channel open-only for a short time.

2.) Na+ rushes in b/c there is a neg. gradient in the cell.

3.) Current is transmitted to adjacent cells.

Phase 0 is the depolarization phase.  It is triggered by depolarizing currents from adjacent cells.  If these currents raise the membrane potential to threshold (usually -70mV), voltage-gated sodium channels open.  These channels are called “fast sodium channels” because they quickly open in response to depolarizing currents, however, they only stay open for a few milliseconds before closing.  While the sodium channels are open, Na+ rushes into the cell due to the electrochemical gradient.  

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The depolarizing current generated in Phase 0 is transmitted to adjacent cells.  These adjacent cells propagate the current by also undergoing depolarization.  Once cells depolarize, they need to return to a state of repolarization so that they can respond to the next depolarizing current.  Phases 1 through 3 restore the cell to its repolarized state

Cardiac Action Potential - myocardial cells

 Phase 1 - the partial repolarization phase 

1.) K+ channels open

2.) K+ moves out of cell to become more negative. 

K+ channels open and the outward movement of K+ causes the interior of the cell to become more negative 

Cardiac Action Potential - myocardial cells

 Phase 2 - the plateau phase

1.) Ca++ channels open & move into the cell.

2.) Slight decrease in membrean potential even though (+) Ca entering cell, 2* outwanrd flow of K. Shows a slight decrease in the membrane potential.

Ca++ channels open and calcium moves into the cell.  the calcium channels are slower to respond to the depolarizing currents that initiated Phase 0; they’re just now opening.

 there’s a slight decrease in membrane potential during this phase even though positively charged calcium ions are entering the cell.  This is because there is a slow outward current of K+ that slightly offsets the Ca2++ influx.  As a result, the membrane potential shows a slight decrease during the plateau phase. 

Cardiac Action Potential - myocardial cells

 Phase 3 - the repolarization phase 

1.) Phase 2 Ca channels close.

2.) K channesl open in phase 1 & 2 stay open.

3.) Causes outward flow of (+) charge inside of cell becomes negative.

4.) increase in the types of K channels open but don't need to know that.

-Repolarization may overshoot restimg membrane potential (hyperpolarization).

During this phase, the calcium channels that were open in Phase 2 close.  However, the potassium channels that were open in Phase 2 remain open.  The result is a net outward flow of positive charge, causing the inside of the cell to b ecome more negative 

Cardiac Action Potential - myocardial cells

 Phase 4 - Return of the cell to its resting membrane potential 

--During phases 0, 1, 2, & part of 3, the cell is refractory to new action potentials. 

--the cell cannot respond to depolarizing currents by propagating action potentials.  The ERP is a protective mechanism because it:

(a) limits the frequency of cardiac contractions,

(b) allows for adequate filling time, and

(c) prevents sustained contractions that can occur in skeletal muscle.    

Pacemaker cells -- SA Node

- No true resting membrane potential-constantly cyling

-spontaneously generate action potentials. 

-sodium is not involved in the generation of pacemaker action potentials.

-Depolarizing currentl carried primarily by relatively slow, inward Ca++ currents

-No fast Na+currentls

Pacemaker cells -- SA Node

Phase 0 - rapid depolarization

1.) Depolarization occurs when voltage-gated Ca⁺⁺ channels    open--> cause the interior of the cell to be less negative.

-These Ca channels are much slower than the Na channels so the slope is less steep than non-pacemaker cells. 

-L-type Ca⁺⁺ channels

Pacemaker cells -- SA Node

Phase 3 - repolarization

(no phase1&2)

1.) Depolarization opens voltage-gated potassium channels and causes a net movement of K+ out of the cell. 

2.) At the same time, the Ca++ channels that opened in Phase 0 begin to close. 

3.) The net result of these two events is to make the interior of the cell more negative, thus contributing to repolarization. 

-At the end of Phase 3, the K+ channels begin to close.

Pacemaker cells -- SA Node

Phase 4 - slow depolarization phase

1.) K channels close so no more K out of cell (cell becomes more negative)

2.) Ca channels open (T-type, transient) in response to low voltage→influx of Ca

3.) Threshold reached, phase 0 initiated.

Disturbances of Cardiac Rhythm

-Transformation of non-pacemaker into pacemaker cells

-Ectopic foci 2* hypoxia

-Damaged tissue (hypoxia) ↑ resting membreane potential. Depolarized cells b/c less negative. Cells don't work as well, damaged→can't maintain int/ext gradient.

-If Na channels can't work, K/Ca channels taker over.

-Non pacemaker action potentials start looking like pacemaker action potentials.

Steps of cardiac contraction:

In phase 1 & 2: K open, some Ca into cell to sarcoplasmic reticulum (SR), which stores Ca

-Ca binds to rhyanodine receptors on surface of SR.

-When they bind, Ca is released from SR.

-Myocyte flooded w/ Ca d/c action potential generated from pacemaker stimulus.

-Ca flooding cell now knock trop off usu keeps activ and myosin from →causes contraction.

Adrenergic Stimulation

 Inotropic effects-myocytes

Catecholamines (NE&Epi) bind to B1

 –NE and epinephrine bind to adenylyl cyclase-coupled G proteins

Adrenergic Stimulation

Chronotropic effects-Pacemaker cells

-How do catecholamines ↑ HR?

-increases intracellular Ac2+ concentration and steepens the slope of phase 1.

-Increases the rate of depolarization.

-Same mechanism happening, ↑Ca, but now occurring in the pacemaker cells.

Adrenergic Stimulation

effects of catecholamines on- Na/K ATPase pump

-When people have ischemic injuries, reparative effects. 

-NE&Epi stim activity of working pumps & ↑activity.

-Repolarizes cell, brings it closer to its original resting membrane potential.

*So epi given in asystole to stimulate pumps that are working→helps restore systole.

Cholinergic Stimulation

Effects of Muscarinic (M2) receptors in heart

*PNS slowing HR

*M2 receptors work to slow the HR after stim actions by the SNS. 

-Slows the speed of depolarization, ↓conduction velocity of AV node.

2.) pacemaker activity can arise from other tissue when there is ischemia or increased catecholamines.

-pacemaker potential from cell other than pacemakers

-↑ voltages, Na channels close quickly.

-Caused by: ↓K, ↑Ca, ↑dig toxicity.

During phase 2, Ca & K channels are open. But if hypercalcemia & Ca going into cell→protective mechanism.

-Ca/Na transporter- 3 Na in, 2 Ca out=net Δ is 1+ charge

-depolarizing cell→closer to threshold→more susceptible to firing in phase 3/4.

-No ATP neede as Δing na/ca closer to conc. gradient

-Net result of hypercalcemis=depolarization, moving closer th tohe threshold, normal stimulus may no make cell fire.

=Spontaneous depolarizations

=response to stimulus lower than normal threshold.

1.) Loop

2.) Uni-directional block→damaged tissue lets signal through one way, blocks other.

3.) Conduction time around ring, must be long enough that it never encounters a cell in a refractory period.

*loop of impulse→tachy or a-flutter

*treat with ablation/cardioversion.

Class 1

Ligand gated Na+ channel blocker

-blocks activated Na channels, affecting the rise of phase 0.

-Ischemic tissue stays in the activated/inactivated refractory state for longer so class1a wants to bind to these states much more.

-Gets on/off Na channels with middle speed.

-also blocks K channels which prolongs repolarization & refractory period.

-Don't give often b/c prodysrhythmic

-Are beta blockers

-Prolong slope Phase 0 and Phase 4-prolong action potentials→↓HR

-Results in decreased heart rate

-Produce negative inotropic effects

-G-protein 

-activate adenalyl cyclase

-↑phosphorylation of proteins→phosphorylation of ca channels→↑ca coming in

-Myocytes:↓ inotropic effects

Pacemaker cells:↓ chronotropic effects b/c blodking cells

-Prolong action potentials by blocking K channels 

-lengthening action potentials→ ↓HR

-Esp. phase 2&3, which prolongs refractory period→repolarization longer

-Increase the effective refractory period of the membrane action potential without altering the phase of depolarization or the resting membrane potential

-Block L-type calcium channels

-Slow conduction through SA and AV node and increase the duration of phase 0 depolarization 

-Can also cause dilation of blood vessels→↓BP b/c Ca dependent

-Inhibition of the Na+/K+ ATPase of the cell membranes

-Therapeutic advantage of inhibiting Na/K pumps. ↑Na inside cell, not pumped out, slows the release of Ca.

-MOre Na in cell, ↑Ca, knock off more trop→↑inotropic effects