CVS 1 previous semester Flashcards
what is the contractile unit of the myocardial cell
sarcomere
what is similar to contractile unit in skeletal muscle
sarcomere
it runs from z line to zline
sarcomere
contains thick filament called
myosin
the sarcomere contains thin filaments called (3)
actin, troponin, tropomyosin
myocardial cells are disarrayed in what condition
hypertrophic cardiomyopathy
in skeletal muscles shortening occurs when what?
thin filament slide along adjacent thick filaments
where do intercalated disk occur
at the end of cells- its the interconnecting nature of cardiac muscle fibers
what do intercalated disks do
maintain cell to cell cohesion
gap junctions or communication junctions are present where?
Are present at the intercalated disks. They are low resistance path between cells that allow for rapid electrical spread of AP
how are the heart cells electrically connected with one another
by gap junctions
the heart behaves as an_____ unit
electrical syncytium
what do T tubules do
carry action potential into the cell interior
what are t tubules and what do they invaginate
are continuous with the cell membrane and invaginate the cells at the z lines
what is the site of storage and release of Ca++ for excitation-contraction coupling
SR
Where do you find the SR in the muscle?
small diameter tubules in close proximity to the contractile elements
what is important in excitation-contraction coupling
calcium
name the 6 sequence of events of excitation. contraction coupling skeletal muscle
AP moves along T-tubule The voltage change is sensed by the DHP* receptor. Is communicated to the ryanodine receptor which opens. Contraction occurs. Calcium is pumped back into SR. Calcium binds to calsequestrin to facilitate storage. Contraction is terminated
Excitation/Contraction Coupling – Cardiac muscle sequence of events 1-5
- AP moves along T-tubule. 2. During the plateau of the AP , Ca++ conductance is increased and Ca++ enters the cell from the extracellular fluid ( inward Ca++ current ) 3. Ca++ then binds to the ryanodine receptor which opens, releasing a large amount of Ca++. (Calcium induced calcium release) 4. Calcium is pumped back into sarcoplasmic reticulum, and back into T-tubule. 5. Contraction is terminated
what is the trigger for SR release in the skeletal muscle
The trigger for SR release is voltage (Voltage Activated Calcium Release - VACR).
the trigger for SR release in the cardiac muscle
The trigger for SR release is calcium (Calcium Activated Calcium Release – CACR).
in the skeletal muscle, what causes the t tubule membrane to open?
The T-tubule membrane has a voltage sensor (DHP receptor)
cardiac muscle - t-tubule membrane has
The T-tubule membrane has a Ca channel (DHP receptor)
what is the ryanodine receptor for skeletal muscle and cardiac muscle
Ca release channel
skeletal muscle ca release is proportional to
membrane voltage
cardiac muscle- the ryanodine receptor ..
The ryanodine receptor is Ca gated and Ca release is proportional to Ca entry.
where does the action potential spread from the cell membrane
into the t tubules
Dihydropyridine receptors
Ca++ conductance is increased and Ca++ enters the cell from the extracellular fluid (inward Ca++ current ) through L-type Ca++ channels
Ryanodine receptors
This Ca++ entry (Ca++ spark ) triggers the release of even more Ca++ from the sarcoplasmic retinaculum (Ca++ induced Ca++ release) through Ca++ release channels
what is the result of calcium coming from the ryanodine receptors
intracellular Ca++ increases
Ca++ binds to ___ , and ____ is moved out of the way removing the inhibition of the actin and myosin binding
Troponin C and Tropomyosin
Actin and myosin bind, the thick and thin filaments slide past each other and the muscle contract. (____)The magnitude of the tension that develops is proportional to the intracellular [Ca++]
power stroke
_____ occurs when Ca++ is reaccumulated by the SR by an active Ca++ ATPase Pump
relaxation
what also moves Ca++ from the cell
by Na+/Ca++ exchanger, Ca++ clears off
calcium channel blockers block which receptors
L-Type Ca++ channels (dihydrophyridine receptors)
what does dantrolene do
Dantrolene (Dantrium®) blocks Ca++ release channels (Ryanodine receptors) on sarcoplasmic retinaculum.
how does norepinephrine act on beta 1 receptors in the heart
increase cAMP which increase Ca++ influx through L-type Ca++ channels leading to increase force of contraction. (Acetylcholine does the opposite)
what is Contractility
the intrinsic ability of the cardiac muscle to develop force
Contractility is related to what intracellular concentration
Is related to intracellular Ca++ concentration
what do we use to estimate contractility
EF (stroke volume/end diastolic volume ) 55%
what do Ve+ inotrops do to contractility
increase contractility
what does -Ve inotrops do to contractility
decrease contractility
Factors that increase contractility (3)
increase heart rate
(Positive staircase: due to increase intracellular Ca++ in a stepwise way, Post-extrasystolic potentiation: due to extra Ca++ entered during extrasystole)
Sympathetic stimulation via b1 receptor increases the inward Ca++ current during the plateau of AP
Digitalis by increasing Ca++ by inhibiting Na+/K+ ATPase
Factors that decrease contractility
Parasympathetic stimulation (Ach) via muscarinic receptor in atria - decreases inward Ca++ flow during the plateau
how does digitalis work on the heart?
Cardiac glycosides (digitalis) increase the force of contraction by inhibiting Na+/K+ ATPase in the myocardial cell membrane. As a result of this inhibition, the intracellular [Na+] increases, diminishing the Na gradient across the cell membrane Na+/Ca++ exchange (a mechanism that extrudes Ca++ from the cell) depends on the size of the Na+ gradient and thus is diminished, producing an increase in intracellular Ca++. Higher the Ca++, more forceful will be the contraction of myocardial cell.
Preload is equivalent to… related to…..
equivalent to end-diastolic volume related to right atrial pressure
Afterload for RV=
For RV = pulmonary artery pressure
Frank-Starling relationship- explain what happens to the heart with greater venous return.
increase venous return (EDV), increase muscle fiber length, increase force of contraction, increase cardiac output The heart will pump what it receives Greater the venous return, the greater the CO
Depolarization
Makes the cell membrane potential less negative due to movement of positively charged sodium ions (Na+) into the cell. increase excitability
Repolarization
Change after depolarization, that returns the membrane potential back to resting potential. Repolarization results from the movement of positively charged potassium ions (K+) out of the cells.
Hyperpolarization
Makes the membrane potential more negative due to movement of negatively charged chloride ions (Cl-) into the cell. decrease excitability
Inward current
Is the flow of positive charge into the cell. Inward current depolarizes the membrane potential.
Outward current
Is the flow of positive charge out of the cell. Outward current hyperpolarizes the membrane potential.
Action potential
Is a property of excitable cells (nerve & muscle) that consists of a rapid depolarization, or upstroke, followed by repolarization of the membrane potential. Action potential have stereotypical size and shape, are propagating and are all-or-none
Threshold
Is the membrane potential at which the action potential is inevitable. At threshold potential, net inward current becomes larger that net outward current. The resulting depolarization becomes self-sustaining and gives rise to upstroke of action potential. If net inward current is less than net outward current, no action potential will occur (i.e. all- or- none response)
Ventricular Muscle Action Potential what is the resting membrane potential value
The resting membrane potential is determined by the conductance to K+ Is equal to -90 mV Is STABLE and of longer duration ~ 300 msec (c.f. neuron AP ~ 1 to 2 msec)
Phase 0- ventricle
Is the rapid upstroke Is caused by transient increase in Na+ conductance leads to inward Na+ movement that depolarizes the membrane.
Phase 1- ventricle
Is brief period of initial repolarization caused by and outward movement of K+
Phase 2- ventricle
Is the plateau of action potential Is caused by transient increase in Ca++ conductance leads to inward movement of Ca++ (L-type Ca++ channels open in this phase) During plateau, Ca++ influx balances K+ efflux. Ca++ influx triggers myocyte contraction
Phase 3- ventricle
Rapid repolarization – massive K+ efflux leads to Hyperpolarization of the membrane Ca++ conductance decreases
Phase 4- ventricular muscle action potential
Is the resting membrane potential – high K+ permeability through K+ channels
what happens to skeletal muscle placed in calcium free solution
nothing
what happens to cardiac muscle placed in calcium free solution
it stops beating
Action Potential in SA node (Pacemaker)
Occurs in SA and AV nodes (SA node is normal pacemaker of heart) Has an UNSTABLE resting potential Exhibits phase 4 depolarization or automaticity
Rate : greater pacemaker to least
Rate : SA node > AV node > His-Purkinje ;
Phase 0- SA node
Is the upstroke of action potential Is caused by an increase Ca++ conductance inward Ca++ influx. These cells lack fast Na+ channels. Results in slow conduction velocity that is utilized by the AV node to prolong transmission from the atria to ventricles
Phase 1 & 2 (plateau) SA node
are absent in the SA node action potential
Phase 3 -SA node
Is repolarization Is caused by an increase K+ conductance outward K+ movement
Phase 4 SA node
Is slow depolarization- membrane spontaneously depolarizes as Na+ conductance increase Accounts for the pacemaker activity of the SA and AV nodes ( automaticity) Is caused by an increase Na+ conductance , which result in an inward Na+ current
Ca++ Channel Blockers examples
Nifedipine, Verapamil , Diltiazem,
Ca++ Channel Blockers MOA
Block voltage dependent L-type Ca++ channels of cardiac and smooth muscles and thereby reduce muscle contractility
Ca channel blockers : Clinical use (5)
Hypertension Angina Arrhythmia (not nifedipine) Prinzmetal’s angina Raynaud’s
Ca channel blockers toxicity
Flushing Dizziness, fatigue Hypotension, headache Constipation
Pharmacolgical therapy of SVT is 1 drug of choice 3 drug alternatives
- IV adenosine - agent of choice; decreases SA and AV nodal activity 2. IV verapamil and IV esmolol or digoxin are alternatives in patients with preserved left ventricular function.
SVT treatment if medication unsuccessful or patient becomes unstable
DC cardioversion if drugs are not effective or if unstable; almost always successful.
For prevention of SVT 1 drug of choice 2 drugs for alternatives
Digoxin is drug of choice Verapamil or beta blockers are alternatives
what is Conduction Velocity
Reflects the time required for excitation to spread throughout cardiac tissue
conduction is slowest in ?
Is slowest in the AV node ( seen as the PR interval on the ECG),
Absolute refractory period (ARP)
NO action potential can be initiated, regardless of how much inward current is supplied
Effective refractory period (ERP)
Is slightly longer than ARP No action potential can be generated
Relative refractory period (RRP)
Is the period immediately after ARP - AP can be elicited , but more than the usual inward current is required
+ve Chronotropic effect =
increase heart rate by increasing the firing rate of SA node
-ve Chronotropic effect =
decrease heart rate by decreasing the firing rate of SA node
+ve Dromotropic effect =
increase conduction velocity through AV node, speeding the conduction of AP from the atria to the ventricles and decreasing the PR interval.
-ve Dromotropic effect =
= decrease conduction velocity through the AV node, slowing the conduction of AP from the atria to the ventricles and increasing PR interval.
Parasympathetic where in the heart in vagal innervation, where is there not vagal innervation
SA node, atria, and AV node have parasympathetic vagal innervation, but the ventricle do not
Sympathetic NE works on which receptor
Neurotransmitter is Norepinephrine which acts on b1 receptor
Heart Rate sympathetic parasympathetic
increase B1 decrease muscarinic
conduction velocity sympathetic parasympathetic
increase B1 decrease muscarinic
contractility sympathetic parasympathetic
increase B1 decrease muscarinic (atria only)
vascular smooth muscle skin, splanchnic- sympathetic effects
constriction a1
vascular smooth muscle skeletal muscle- sympathetic
relaxation B2
sa node phase 0
depolarization inward ca current
sa node phase 3
outward K current
sa node phase 4
slow depolarization inward na current
action potential in sa node add epinephrine
phase 4 depolarization is accelerated,
Preload
increase venous return, increase end diastolic volume, increase length of ventricular muscle fibers
after load lv=?
aortic pressure
increasing arterial pressure will…
increase after load
what is the effect of parasympathetic stimulation on phase 4 of the sa node action potential
decreasing heart rate-decreases rate of phase 4 depolarization
what is the effect of sympathetic stimulation on phase 4 of the sa node action potential
increases HR increasing rate of phase 4 depolarization
vascular smooth muscle calcium channel blockers greatest to least
Vascular smooth muscles : nifedipine > diltiazem > verapamil
Heart- calcium channel blockers greatest to least
Heart : verapamil > diltiazem > nifedipine (Verapamil = Ventricle)
ARP of the ventricle muscle
ARP of ventricular muscle is 250msec
why does the conduction need to be slow in the AV node.
allowing time for ventricular filling before ventricular contraction.
what happens in the conduction through the av node is fast
If conduction velocity through the AV node is increased, ventricular filling may be compromised.
av node and HPS are considered?
AVN&HPS are latent pacemakers
which ventricle phase is reduced by calcium channel blockers
phase 2
what receptor does acetylcholine stimulate on the heart
Neurotransmitter is Acetylcholine which acts on muscarinic receptors
parasympathetic stimulation effects on the heart and decreases which phase
decrease HR by slowing rate of phase 4 depolarization decrease conduction velocity through AV node, increase PR interval
sympathetic stimulation effects on the heart increasing which phase
increase HR by accelerating rate of phase 4 depolarization increase conduction velocity through AV node, decrease PR interval
define excitability
Is the ability of cardiac cells to initiate AP in response to inward depolarizing current
Absolute refractory period (ARP) when does it begin and end
Begins with the upstroke of the AP and ends after the plateau
where is conduction velocity fastest
Purkinje system
what is this from
parasympathetic stimulation- due to increase permability to K
−Due to the permeability to Na+ and Ca++
what is this picture of
normal firing
Name 4, 0, 3
• Phase 4 (slow depolarization)
−inward Na+ current
• Phase 0 (depolarization)
−Inward Ca++ current
• Phase 3
−outward K+current
Name 0, 1, 2, 3, 4
Phase 0- rapid upstroke-Fast Na+ channels open, inward Na+ flow
Phase 1- initial repolarization- K+ channels open, outward K+ flow
Phase 2- plateau-Ca++ channels open, inward Ca++ flow
Phase 3- rapid repolarization- K+ channels open more, massive outward K+ flow
Phase 4- Resting membrane potential- high K+ permeability through leaky K+ channels
Name the three boxes
