L15/16 Cardiac Electrophysiology And Excitation-Contraction Flashcards
Cardiac muscle
Striated
ANS involuntary
Multi-nucleated
Junctions
Large mitochondria
Intercalated discs
Connect adjacent cardiac muscle fibers and form function syncytium
Two kinds of membrane junctions within them:
Desmosomes-mechanical junctions
Gap junctions- electrical junctions
Cardiac muscle looks similar to
Skeletal muscle
Sarcolemma
T-tubules
SR sacks
Sequence of electrical events in the heart
SA node AV node Bundle of His Bundle branches (left and right) Purkinje fibers
Only way to guarantee ventricles aren’t contracting while atria are
Isolating electrical activity from one part of the heart from the other
Controls when ventricles get activated compared to atria
Bundle of his
On pathway between atria and ventricles
Delay in conduction of activity btw AV node and ventricles
Conduction of the cardiac AP
Atria - fast
AV node - slows down
His-purkinje - fastest
Ventricle - back to atria velocity
Due to how fast AP can depolarize and depolarize
AV node delay
AV node to bundle of his is Only point of electrical contact btw atria and ventricle
Very slow conduction
Allows adequate time for ventricular filling btw beats
Essential to synchronize atria and ventricular contractility
Purkinje fibers
Mesh of specialized fibers with very fast conduction
Rapidly spread impulse throughout much of left and right ventricles
Allows for efficient contraction and ejection of blood
Overdrive suppression
Phenomenon by which SA node drives heart rate and suppresses the latent pacemakers
Wait for impulses to be retrieved
SA node has
Fastest intrinsic firing rate
Damage to SA node, AV node may have control over heart rate
Ectopic pacemaker (ectopic focus)
Occurs when the latent pacemakers have an opportunity to drive the heart rate ONLY if
SA node firing rate decreases (vagal stimulation)
SA node firing stops completely (SA node destroyed, removed, etc)
Intrinsic firing of latent pacemakers become faster
Conduction of APs from SA node is blocked by disease
Types of myocardial cells
Pacemaker (nodal) cells
Conductile cells
Contractile cells
Pacemaker (nodal) cells
Pacemaker activity
Slow action potentials
SA node (primary) AV node
Conductile cells
Rapid spread of electrical signal
FAST AP
bundle of his
Purkinje fibers
No myosin or action
Contractile cells
Contraction (pumping)
FAST AP
Ventricular and atrial cells
Contain myosin and action
Phases of fast AP
Phase 0: upstroke (similar to skeletal muscle AP) fast inward Na+ current
Phase 1: early repolarization
Transient K+ channels (Ito; outward)
Phase 2: plateau phase
L-type Ca2+ channel inward (depolarizes) and K+ (Ito, Ik, Ik1) currents outward (hyperpolarize)
Phase 3: repolarization
turn-off Ca current and increases K current
Phase 4: resting potential
Caused by large background K current
Resting membrane potential of heart
-90
Due to many more leaky K channels (high permeability to K at rest)
Phases of slow AP
Phase 0: upstroke
L-type Ca channel ( NOT Na - capacity lower)
Phase 1 and 2: absent
Phase 3: repolarization
K current
Phase 4: pacemaker potential (spontaneous depolarization)
“Funny” Na current (If) and a T-type (transient) Ca current
Relationship of AP and refractory period to the duration of the contractile response in cardiac muscle
Because long refractory period occurs in connecting with prolonged plateau phase
Summation and that is of cardiac muscle is impossible
Ensures alternate periods of contraction and relaxation which are essential for pumping blood
Excitation-contraction coupling in cardiac contractile cells
- Excitation AP causes depolarization of the membrane (Travels down T tubule)
- Entry of small amount Ca from ECF through L-type Ca channels
- Ca enters cell
- Ca-induced Ca release from SR (essential)
- SR releases large amount Ca through ryanodine receptors. Cytosolic Ca levels increase
- Ca binds troponin-tropomyosin complex in thin filaments pulled aside
- Cross bridge cycling btw thick and thin filaments
- Contraction
Ca induced Ca release in cardiac muscle
Ca enters through L type Ca channel
Ryr receptor is close proximity to L type Ca channel but not physical connection
Necessary for contraction
Mechanism for decreasing intracellular Ca in cardiac muscle
Decrease in contractile force occurs when conc intercellular Ca decreases
Cytosolic Ca conc decrease by:
SR Ca ATPase (SERCA)
Sarcolemmal Na/Ca exchanger (NXC)
Sarcolemmal Ca ATPase
Need Na/K ATPase for NCX
Length tension relationship in cardiac muscle
Neither summation nor recruitment occurs
Force contraction is altered in others ways
Does not normally function at peak of Lo
Rather works in ascending limb
stretching cardiac muscle fibers (to a point) increase contraction
Force developed by contraction depends on initial fiber length
Positive inotropic effect
Increase in contractility that involves an increase in the amount tension developed
Also an increased rate of tension development at a given fiber length
Negative inotropic effect
Decrease in contractility that involves decrease in tension developing and a decrease in the rate of tension development at given fiber length
Contractility state in cardiac muscle
Regulation of Ca flux from modulation of the L-type calcium channels and SR
A single AP provides sufficient free cytoplasmic ca to activate (at most) about 1/2 crossbridges
How does heart function change?
Heart rate - chronotropy
AV conduction - dromotrophy
Electro-mechanical coupling - contractility - inotropy
Autonomic effects in heart rate
SA node peacemaker activity
Sympathetic simulation - increase rate of phase 4 depolariziaton and increases frequency of AP
Parasympathetic- decreases rate of phase 4 depolarization and hyperpolarizes the maximum potential to decrease the frequency of AP
SNS has what effect on contractility/inotrophy
Positive inotropic effect
Increased peak tension
Increased rate of tension development
Faster rate of relaxation (shorter contraction, more time for filling)
Mediated via beta1 receptors coupled with G protein to adenylyl cyclase
Increased cAMP
Activation of protein kinase A
Phosphorylation of proteins
Phosphorylation of sarcolemma Ca channels
Increases Ca in cells , stronger contraction
Phosphorylation of phospholamban (on SERCA) drives Ca back into SR and always relaxation to happen faster
PSNS has what effect on contractility/ inotropy
Negative inotropic effect on atria
Via muscarinic receptors coupled to G protein (inhibitory Gk) to adenylyl cyclase
Decreases cAMP
Reduced inward Ca current by AP plateau ACh
Increases IkACh thereby shortening the duration of AP and indirectly decreases inward Ca current (by shortening plateau phase)
Decrease Ca induced Ca released from SR
PNS
M receptors
Decrease cAMP
Reduces Ca induced Ca release from SR
CO to ventricular end diastolic volume
More volume , more CO
Fight/ flight increase CO (pos inotropic)
Rest/digest decrease CO (neg inotropic)
Extra systole
Extra heart beat
Following beat goes up (more tension)
Extra heart beat allows more Ca to be released
And the following heartbeat tension goes up because now Ca induced Ca release adds to intercellular space Ca
Common cardiac drugs
Na-K ATPase blocker
Ca-channel blockers
Beta-receptor agonists
Na-K ATPase
Inhibits Na/K ATPase which increases the ICF Na concentration
Therefore reversing Na/Ca exchanges leading to higher intracellular [Ca]
Enhances contractility (pos inotropy)
Used in patients w contractility issues
Ca-channel blockers
L type
Vascular effects:
Smooth muscle relaxation (vasodilation)
Hypertension
Cardiac effects:
Decreased contractility (neg inotropy) angina
Decreased heart rate (neg inotropy) angina
Decreased conduction velocity (neg dromotropy)
Beta-agonists and contractility
Pos inotropy via cAMP pathway
Congestive heart failure, heart attack
Used to enhance contractility of the heart
