Download Contractile cells

PHYSIOLOGY OF CARDIAC
MUSCLE
PHYSIOLOGICAL PROPERTIES OF CARDIAC
MUSCLE
• Excitability: ability to respond to an electrical impulse
• Excitation - the process of generation of action potential
• Excitability - the ability to generate an action potential
• Automaticity: ability to initiate an electrical impulse
• Conductivity: ability to transmit an electrical impulse from one cell to
another
• Contractility is a term used to denote the force generated by the
contracting myocardium under any given condition
The Heartbeat
• What Two Types of Cardiac Cells are Needed for
the Heartbeat?
• Contractile cells
• Provide the pumping action
• Cells of the conducting system
• Generate and spread the action potential
EXCITABILITY
Myocardial Physiology
Contractile Cells
• Special aspects
• Intercalated discs
• Highly convoluted and interdigitated junctions
• Joint adjacent cells with
• Desmosomes & fascia adherens
• Allow for synticial activity
• With gap junctions
• More mitochondria than skeletal muscle
• Less sarcoplasmic reticulum
• Ca2+ also influxes from ECF reducing storage
need
• Larger t-tubules
• Internally branching
• Myocardial contractions are graded!
Myocardial Physiology
Contractile Cells
• Special aspects
• The action potential of a contractile cell
• Ca2+ plays a major role again
• Action
potential is longer in duration than a “normal” action potential due to
2+
Ca entry
• Phases
4 – resting membrane potential @ -90mV
0 – depolarization
• Due to gap junctions or conduction fiber action
• Voltage gated Na+ channels open… close at 20mV
1 – temporary repolarization
• Open K+ channels allow some K+ to leave the cell
2 – plateau phase
• Voltage gated Ca2+ channels are fully open (started during initial
depolarization)
3 – repolarization
• Ca2+ channels close and K+ permeability increases as slower activated
K+ channels open, causing a quick repolarization
• What is the significance of the plateau phase?
Myocardial Physiology
Contractile Cells
The action potential of a
contractile cell Ca2+ plays a
major role again
Action potential is longer in
duration than a “normal”
action potential due to
Ca2+ entry
Myocardial Physiology
Contractile Cells
Phases
4 – resting membrane
potential @ -90mV
The inward current that
balances this outward current
is carried by Na+ and Ca2+, even
though the conductances to
Na+ and Ca2+ are low at rest.
Myocardial Physiology
Contractile Cells
Phases
0 – depolarization
Due to gap junctions or
conduction fiber action
Voltage gated Na+ channels
open… close at 20mV
Myocardial Physiology
Contractile Cells
Phases
1 – temporary repolarization
Open K+ channels allow some
K+ to leave the cell
Myocardial Physiology
Contractile Cells
Phases
2 – plateau phase
Voltage gated Ca2+ channels
are fully open (started during
initial depolarization)
Myocardial Physiology
Contractile Cells
Phases
3 – repolarization
Ca2+ channels close and K+
permeability increases as
slower activated K+ channels
open, causing a quick
repolarization
Myocardial Physiology
Contractile Cells
Skeletal Action Potential vs Contractile
Myocardial Action Potential
Myocardial Physiology
Contractile Cells
• Plateau phase prevents summation due to the
elongated refractory period
• No summation capacity = no tetanus
• Which would be fatal
AUTOMATICITY
• property automatic - the ability to spontaneously excited
• SA node:
• Demonstrates automaticity:
• Functions as the
pacemaker.
• Spontaneous depolarization
(pacemaker potential):
• Spontaneous diffusion
caused by diffusion of
Ca2+ through slow Ca2+
channels.
• Cells do not maintain
a stable RMP.
Myocardial Physiology
Autorhythmic Cells (Pacemaker Cells)
• Characteristics of Pacemaker
Cells
• Smaller than contractile cells
• Don’t contain many myofibrils
• No organized sarcomere
structure
• do not contribute to the
contractile force of the heart
conduction myofibers
normal contractile myocardial
cell
SA node cell
AV node cells
Myocardial Physiology
• Characteristics of Pacemaker Cells
Autorhythmic Cells (Pacemaker Cells)
• Unstable membrane potential
• “bottoms out” at -60mV
• “drifts upward” to -40mV, forming a pacemaker potential
• Myogenic
• The upward “drift” allows the membrane to reach threshold potential (-40mV) by itself
• This is due to
1. Slow leakage of K+ out & faster leakage Na+ in
• Causes slow depolarization
• Occurs through If channels (f=funny) that open at negative membrane
potentials and start closing as membrane approaches threshold potential
2. Ca2+ channels opening as membrane approaches threshold
• At threshold additional Ca2+ ion channels open causing more rapid
depolarization
• These deactivate shortly after and
3. Slow K+ channels open as membrane depolarizes causing an
efflux of K+ and a repolarization of membrane
• Altering Activity of Pacemaker Cells
Myocardial Physiology
• Sympathetic activity
Autorhythmic Cells (Pacemaker Cells)
• NE and E increase If channel activity
• Binds to β1 adrenergic receptors which
activate cAMP and increase If channel
open time
• Causes more rapid pacemaker potential
and faster rate of action potentials
Sympathetic Activity Summary:
increased chronotropic effects
heart rate
increased dromotropic effects
conduction of APs
increased inotropic effects
contractility
• Altering Activity of Pacemaker Cells
• Parasympathetic activity
Myocardial Physiology
Autorhythmic Cells (Pacemaker Cells)
• ACh binds to muscarinic receptors
• Increases K+ permeability and decreases
Ca2+ permeability = hyperpolarizing the
membrane
• Longer time to threshold = slower rate
of action potentials
Parasympathetic Activity Summary:
decreased chronotropic effects
heart rate
decreased dromotropic effects
 conduction of APs
decreased inotropic effects
 contractility
Rhythm of Conduction System
• SA node fires spontaneously 90-100 times per minute
• AV node fires at 40-50 times per minute
• If both nodes are suppressed fibers in ventricles by
themselves fire only 20-40 times per minute
• Atrioventricular bundle of His
• Ventricular tissue fires at 20-40 beats/minute and can
occur at this point and down
• Artificial pacemaker needed if pace is too slow
• Extra beats forming at other sites are called ectopic
pacemakers
• caffeine & nicotine increase activity
Normal pacemaker activity
• various autorhythmic cells have different rates of depolarization to threshold –
so the rate of generating an AP differs
• AP propagated through gap junctions or through the conduction system of the
heart
• contraction rate is driven by the SA node – fastest autorhythmic tissue
failure of SA node
blockage of transmission from SA through the AV node
• in some cases – the normally slowest Purkinje fibers can become overexcited = ectopic focus
• premature APs
• premature ventricular contraction (PVC)
• occurs upon excess caffeine, alcohol, lack of sleep, anxiety and stress
• some organic conditions can also lead to this
Cardiac Conduction
Conducting Tissues of the Heart
• APs spread through myocardial cells through gap junctions.
• Impulses cannot spread to ventricles directly because of
fibrous tissue.
• Conduction pathway:
• SA node.
• AV node.
• Bundle of His.
• Purkinje fibers.
• Stimulation of Purkinje fibers cause both ventricles to
contract simultaneously.
Conduction System of Heart
• gap junctions – two PMs are connected by a “channel” made
of specific proteins = connexons
• connexons are 6 protein subunits that form a hollow tube-like
structure
• two connexons join end to end to connect the cells
• allow a free flow of materials from cell to cell
• allow for the spread of electricity within each atrium and
ventricle
• no gap junctions connect the atrial and ventricular contractile
cells – block to electrical conduction from atria to ventricle!!!
• also a fibrous skeleton the supports the valves –
nonconductive
• therefore a specialized conduction system must exist to allow
the spread of electricity from atria to ventricles
Intrinsic conduction system
1. Intrinsic conduction system
▪ Built into heart tissue & sets basic rhythm
▪ Pacemaker = Sinoatrial (SA) Node
Sequence of action:
1.Sinoatrial (SA) node – right atrium
• Generates impulses  Starts each heartbeat
2.Atrioventricular (AV) node – between atria & ventricles
• Atria contract
3.Bundle of His (or AV bundle)
4.Bundle branches – interventricular septum
5.Purkinje fibers – spread within ventricle walls
• Ventricles contract
Conduction of Impulse
• APs from SA node spread quickly at rate of 0.8
- 1.0 m/sec.
• Time delay occurs as impulses pass through AV
node.
• Slow conduction of 0.03 – 0.05 m/sec.
• Impulse conduction increases as spread to
Purkinje fibers at a velocity of 5.0 m/sec.
• Ventricular contraction begins 0.1–0.2 sec.
after contraction of the atria.
• atrial conduction
system/interatrial pathway –
spread of electricity from right
to left atrium ending in the LA
• through gap junctions of the
contractile cells
• internodal pathway – spread of
electricity to the AV node via
autorhythmic cells
• SA to AV node – 30msec
• BUT spreads relatively slowly
through the AV node
• this allows for complete filling
of the ventricles before they
are induced to contract = AV
nodal delay
• ventricular conduction system
(Purkinje system) – Bundles of His
and Purkinje fibers
• travel time = 30 msec
• PFs conduct impulse 6 times
faster than the ventricular muscle
cells would on their own
• the PFs do not connect with
every ventricular contractile cell
• so the impulse spreads via gap
junctions through the ventricle
muscle – similar to the atrial
system
• diffusion through the PFs allow
for simultaneous contraction of
all ventricular cells
Cardiac excitation
efficient cardiac function requires three criteria
• 1. atrial excitation and contraction should be complete before ventricular excitation and
contraction
• opening and closing of valves within the heart depend upon pressure – which is generated
by muscle contraction
• so simultaneous contractions of atria and ventricles would lead to permanent closure of
the AV valves – myocardium of the ventricles is larger and stronger
• normally – atrial excitation and contraction occurs about 160 msec before ventricular
• 2. cardiac fiber excitation should be coordinated to ensure each chamber contracts as a unit
• muscle fibers cannot become excited randomly
• role of the gap junctions
• 3. atria and ventricles should be functionally coordinated
• atria contract together, ventricles contract together
• permits efficient pumping of blood into the pulmonary and systemic circuits
• uncontrolled excitation and contraction of ventricular cells – fibrillation
• correction by:
• 1. electrical defibrillation
• 2. mechanical defibrillation
Electrocardiogram---ECG or EKG
• electrical currents generated by the heart
are also transmitted through the body
fluids
• can be measured on the surface of the
chest
• therefore it is not a direct measurement of
the actual electrical conductivity of the
heart itself
• represents the overall spread of activity
through the heart during depolarization –
sum of all electrical activity
• measured through the placement of 6
leads on the chest wall (V1 – V6) PLUS 6
limb leads (I, II, III, aVR, aVL and aVF)
Electrocardiogram---ECG or EKG
• it's usual to group the leads according to
which part of the left ventricle (LV) they
look at.
• AVL and I, as well as V5 and V6 are
lateral, while II, III and AVF are inferior.
• V1 through V4 tend to look at the
anterior aspect of the LV
Electrocardiogram---ECG or EKG
• P wave
• atrial depolarization
• SA depolarization is too weak to measure
• smaller than the QRS complex due to the smaller size
of the atrial muscle mass
• will be affected by abnormalities in the pacemaker
activity of the SA node
• PR segment/PQ interval – AV nodal delay
• P to Q interval
• conduction time from atrial to ventricular excitation
• no net current flow within the heart musculature &
the flow through the AV node is too small to
measure– baseline
• if activity in the AV node is abnormal – this interval ill
be affected
Electrocardiogram---ECG or EKG
• QRS complex
• ventricular depolarization
• will be affected by the appearance of an ectopic
focus (region of hyperactive ventricular contraction)
• ST segment – time during which ventricles are
contracting and emptying
• ventricles are completely depolarized and the cells
are in their plateau phase
• T wave
• ventricular repolarization
• TP interval
• time during which ventricles are relaxing and filling
CONTRACTILITY
Myocardial Physiology
Contractile Cells
• Initiation
• Action potential via pacemaker cells to conduction
fibers
• Excitation-Contraction Coupling
1. Starts with CICR (Ca2+ induced Ca2+ release)
• AP spreads along sarcolemma
• T-tubules contain voltage gated L-type Ca2+
channels which open upon depolarization
• Ca2+ entrance into myocardial cell and opens RyR
(ryanodine receptors) Ca2+ release channels
• Release of Ca2+ from SR causes a Ca2+ “spark”
• Multiple sparks form a Ca2+ signal
•
•
Excitation-Contraction Coupling cont…
2. Ca2+ signal (Ca2+ from SR and ECF) binds to troponin
Myocardial
to initiate myosin head attachment to actin
Contractile Cells
Contraction
• Same as skeletal muscle, but…
• Strength of contraction varies
• Sarcomeres are not “all or none” as it is in
skeletal muscle
• The response is graded!
• Low levels of cytosolic Ca2+ will not
activate as many myosin/actin
interactions and the opposite is true
• Length tension relationships exist
• Strongest contraction generated
when stretched between 80 &
100% of maximum (physiological
range)
• What causes stretching?
• The filling of chambers
with blood
Physiology
Cardiac Cycle
Cardiac Cycle
Phases
• Systole = period of contraction
• Diastole = period of relaxation
• Cardiac Cycle is alternating periods of
systole and diastole
Cardiac cycle
• A. Midventricular diastole
• during most of the ventricular
diastole, the atrium is also in
diastole = TP interval on the EKG
• as the atrium fills during its
diastole, atrial pressure rises and
exceeds ventricular pressure (1)
• the AV valve opens in response to
this difference and blood flows
into the right ventricle
• the increase in ventricular volume
rises even before the onset of
atrial contraction (2)
Cardiac cycle
• B. Late ventricular diastole
• SA node reaches threshold and fires its impulse to the AV
node = P wave (3)
• atrial depolarization results in contraction – increases the
atrial pressure curve (4 – green line)
• corresponding rise in ventricular pressure (5 – red line)
occurs as the ventricle fills & ventricular volume increases
(6)
• the impulse travels through the AV node
• the atria continue to contract filling the ventricles
• C. End of ventricular diastole
• once filled the ventricle will start to contract and enter its
systole phase
• ventricular diastole ends at the onset of ventricular
contraction
• atrial contraction has also ended
• ventricular filling has completed
• ventricle is at its maximum volume (7) = end-diastolic
volume (EDV), 135ml
Cardiac cycle
• D. Start of ventricular systole
• at the end of this contraction is the onset
of ventricular excitation (8) = QRS
complex
• the electrical impulse has left the AV
node and enters the ventricular
musculature
• this induces ventricular contraction
• ventricular pressure will begin to rise
rapidly after the QRS complex (red line)
• this increase signals the onset of
ventricular systole (9)
• atrial pressure is at its lowest point as its
contraction has ended and the chamber is
empty (green line)
• the ventricular pressure now exceeds
atrial – AV valve closes
Cardiac cycle
• E. isovolumetric ventricular contraction
• ventricular pressure also opens the semilunar valves
• however, just after the closing of the AV and opening of the SL is a brief moment
where the ventricle is a closed chamber (10) = isovolumetric contraction
• ventricular pressure continues to rise (red line) but the volume within the
ventricle does not change (11)
• F. Ventricular ejection
• ventricular pressure will now exceed aortic pressure as the ventricle continues is
contraction (12)
• aortic SL is forced open and the ventricle empties
• this volume of blood – stroke volume (SV)
• the ejection of blood into the aorta increases its pressure (aortic pressure) and
the aortic pressure curve rises (13 – purple line)
• ventricular volume now decreases (14 – blue line)
• F. End of ventricular systole
• as the ventricular volume drops
• BUT ventricular pressure continues to rise as the contraction increases its force
(red line) – then starts to decrease as blood begins to be ejected
• at the end of the systole there is a small volume of blood that remains in the
ventricle – end-systole volume (ESV), 65ml (15)
• EDV-ESV = SV (point 7 – point 15)
• G. Ventricular repolarization
• T wave – point 16
• as the ventricle relaxes – ventricular pressure falls below aortic and the aortic SL
closes (17)
• this closure produces a small disturbance in the aortic pressure curve – dicrotic
notch (18)
Cardiac cycle
• H. Isovolumetric ventricular relaxation – Start of Ventricular
Diastole
• all valves are closed because ventricular pressure still
exceeds atrial pressure – isovolumetric relaxation (19)
• chamber volume remains constant (20)
• I. Ventricular filling/MidVentricular Diastole
• as VP falls below AP – the AV valve opens again (21) and
ventricular filling starts again increasing ventricular
volume (blue line)
• as the atria fills from blood from the pulmonary veins
(lungs) it increases AP
• with the AV valve open this blood fills the ventricle
rapidly (23)
• then slows down (24) as the blood drains the atrium
• during this period of reduced filling, blood continues to
come in from the pulmonary veins – goes directly into
the ventricle
• cycle starts again with a new SA depolarization
Heart Sounds
• Closing of the AV and
semilunar valves.
• Lub (first sound):
• Produced by closing of the AV
valves during isovolumetric
contraction.
• Dub (second sound):
• Produced by closing of the
semilunar valves when
pressure in the ventricles falls
below pressure in the
arteries.