Cardiovascular Systems Physiology and Pathophysiology II Flashcards
Cardiac APs are initiated within nodal tissues and are conducted through the bundle branches to the
Myocardium
What channels enable inward Ca2+ and Na+ (funny current) and outward K+ in the SA node?
-Pacemaker Potentials
T-type Ca2+ channels, Na+ HCN channels, and K+ channels
To begin one pacemaker cycle, a gradual depolarization is enabled by
Inward Ca2+ and Na+ and outward K+
During the gradual depolarization, the membrane potential creeps upward, becoming less negative and reaching around
-55 mV
What happens at around -55 mV?
T-type Ca2+ channels are increasingly activated
The increasing activation of T-type Ca2+ channels in a pacemaker potential produces a rapid upstroke in
Action potential
HCN and Ca2+ channels are inactivated, shutting down If, and thus allowing repolarization via K+ efflux at about
0 mV
Repolarization leads to a brief period of hyperpolarization which is necessary to reactivate
HCN channels
In a cardiomycete depolarization-repolarization plateau potential (different from pacemaker potential) phase 0 is dependent upon
Na+ influx
The rapid, Na+ dependent depolarization of cardiac muscle is followed by phase 1, which is a
Transient K+ dependent repolarization
On the sarcolemma, the Na+ dependent AP also activates
Votage gated- Ca2+ channels (Type L)
Increased intracellular Ca2+ stimulates the release of
Ca2+ via activation of
-called calcium induced calcium release
Ryanodine receptors within SR
Elevations in sarcoplasmic Ca2+ from extracellular (via type L channels) and intracellular (from the SR) sources is represented by phase 2 which is the
Plateau phase
To complete the cycle of cardiac muscle AP, phase 2 is followed by phase 3 which is a
Rapid K+ dependent repolarization
Phase 4 of the plateau potential is a
Slight efflux of K+
Type L channels are very interesting proteins. Not only are they voltage-gated, but they are also functionally coupled to
Type B1 and B2 adrenergic receptors and Cholinergic-muscarinic (ACh) receptors (type M2)
Because of this complex triad motif, the fundamental activation of type L channels is dependent upon the
Na+ induced AP
Also, the L type Ca2+ channel activity is modulated by
Catecholamines and ACh
The predominant beta adrenergic isoform expressed in a healthy heart, and are coupled to the stimulation of the G protein-adenylyl cyclase-dependent production od cAMP and PKA signalling cascades
B1 receptors
This signal transduction pathway activates L channels; thus, promoting
Ca2+ influx
Also facilitate L channel activation but activation of this receptor can also induce lusitropy
B2 receptors
Increased rate of relaxation that is medicated by mobilization of Gi protein dependent signaling
Lusitropy
An increase in the dominance of cardiac B2 activity plays a role in the pathogenesis of certain forms of
Heart failure
Activated in the presence of elevated sacoplasmic Ca2+ concentrations
Troponin C
Binds Ca2+ and causes a conformational change in the troponin-tropomyosin complex that reveals the myosin binding sites within actin
Troponin C
Increased PKA signaling induces a triple response in cardiac myocytes. These responses are
- ) Activation of type L channels
- ) Phospholamban is phosphorylated by PKA
- ) PKA mediates the phosphorylation of troponin I
Intracellular protein with a stimulatory effect on SERCA, which cause rapid re-sequestration of Ca2+ into the SR
Phospholamban
Reduces the affinity of troponin C for Ca2+
Activated (phosphorylated) troponin I
Causes an increase in the rate of cardiac pumping by causing changes in intracellular Ca2+
Adrenergic activation of cAMP/PKA signaling
Binds to and activates cholinergic M2 receptors, which interrupts the activation of type L channels and slows cardiac muscle contractility
ACh
The primary intrinsic cardiac pacemaker; as directed by ANS input, it controls increases and decreases in HR based upon metabolic demand
The SA node
In absence of other mediation, the SA node fires to cause approximtely
80-100 beats per minute
The chronic component of the SA node and decreases the rate of SA node firing
PSNS
The PSNS sets the basal (resting) HR by suppressing the frequency of
SA node AP
Preganglionic fibers of the PSNS originate within the medulla in the
DMV and NA
Preganglionic PSNS fibers travel via the right and left vagus, and synapse with post-ganglionic fibers within the heart, very near the
SA and AV nodes
The SA node is mainly innervated by fibers from the
Right vagus nerve
What effect would an increase in right vagal PSNS activity have?
Decreased SA node firing
SA nodal tissue contains voltage-dependent (T-type) Ca2+ channels that are:
- ) Activated by?
- ) Suppressed by?
- ) Adrenergics
2. ) ACh
These specialized T-type Ca2+ channels contain two gates (f and d), that when open enable Ca2+ influx and depolarization of the
SA node
What happens to the f and d gates upon membrane depolarization?
- ) f gates gradually close
2. ) d gates gradually open
The optimal membrane voltage for maximal percent open f and d gates is approximately
-40 mV
As f gates close, Ca2+ current diminishes, but at this time there is a stimulation of an
Outward K+ current
The repolarization that is induced by K+ efflux stimulates the influx of
Na+ through HCN channels (the pacemaker current)
The cycle of Na+ influx, slow Ca2+ influx, K+ outflux, and Na+ influx through HCN channels is a self perpetuating mechanism and is identified as a
Pacemaker current
Activates ligand-gated K+ channels; in so doing, driving membrane potential more negative and inducing a slower depolarization
ACh
This occurs via the ACh-mediated activation of Type 2 cholinergic-muscarinic receptors (CM2) within the
SA node
In response to CM2 activation by ACh, the βƴ subunit of specific G proteins are coupled to the activation of
Outward rectifying K+ channels
Outward IK+ essentially clamps membrane potential
near the equilibrium potential for K+, and in so doing Impedes depolarization, slows SA nodal firing, and thus
slows HR
Activation of PSNS fibers suppresses both the slow inward Ca2+ current and If; thereby, lowering the rate of rise of the pacemaker current and dampening the
Rate of SA firing
Increase the rate and magnitude of SA nodal APs by augmenting the inward Na+ (If) and Ca2+
SNS neurotransmitters
Demonstrates the same general phases as are observed in ventricular myocytes
Atrial myocyte depolarization
What has a shorter duration, the plateau phase of an atrial AP or a ventricular AP?
Artial AP
Performs intrinsic pacemaker and key interface functions between the atria and ventricles
AV node
The only electrical connection between the atria and ventricles
AV node
A healthy AVnode will only allow unidirectional conduction of AP from the atria to the
His bundle
In the absence of normal regulatory mechanisms, the AV node independently will fire at approximately
40-50 beats per minute
The main difference between the AV nodal AP and the SA nodal AP is that the AV nodal AP also has slow
L-type Ca2+ channels
-SA node only has T-type (which AV also has)
The presence of slow (L-type) Ca2+ in addition to
type T Ca2+ channels, enables the phenomenon of
AV nodal delay (long time interval between AV nodal APs)
Type-L Ca2+ channel antagonists which are specific for the type-L Ca2+ channels expressed in the heart
Diltiazem and verapamil
What effect do diltiazem and verapamil have on AV conduction?
Slow AV conduction and have a negative inotropic effect
The relatively slower pacemaker ability of the AV node is accounted for by considering that relative to the SA node, the AV node has a much slower generation of the
Funny current (Na+ influx from HCN)
The AV node is innervated by post-ganglionic PSNS fibers from the
Left vagus nerve
Therefore, an increase in left PSNS vagal activity would be correlated with a
Decrease in frequency of AV nodal APs
The bridge between the AV nodal relay and the ventricular myocardium
The His-Purkinje system
Work with the AV node to ensure optimal relay of conduction between the atria and ventricles
His fibers
Fast conducting tracts that coordinate ventricular contraction
Purkinje fibers
Conduction via a normal His-Purkinje system leads to so-called
Narrow complex QRS
That is, conduction via normal His-Purkinje system results in the duration of the QRS complex being
Less than 120 msec in duration
The characteristics of His-Purkinje APs resemble those generated within the myocardium, with the addition of a very slow
Phase 4 pacemaker current (If)
In the event of a complete block in AV nodal relay, there can be a generation of an escape pacemaker of approximately
20-40 bpm
The AV node is functionally coupled to the
Central bundle of His
The central bundle divides into the right and left bundle branches, which in turn give rise to the
Purkinje fibers
The Purkinje network itself has an intrinsic pacemaker activity that can support approximately
15-20 bpm
Purkinje fiber AP is similar to that previously described in SA and AV nodal tissue, with the exception of a
Predominant phase 1 and an intermediate phase 2
The characteristics of the Purkinje AP enable a relatively long
Refractatory period
This long refractatory period serves as a buffer/modulator in response to
Rapid atrial induced APs
The refractatory period of Purkinje fibers is inversely correlated with
HR
Under basal conditions, impulses are modulated within the SA node by the
PSNS
Upon generation of SA nodal AP, the signal spreads radially through the atrial myocardium to the
AV node
From the AV node, signals are relayed through the bundle of His to the right and left bundle branches, downward, to the apex region of the
Ventricles
From there, APs are propagated upward via the
Purkinje fiber network
This induces a highly coordinated depolarization (contraction) of ventricular myocardium from
Apex to base
Mistiming of depolarization which can occur without noticeable disruption of the normal cardiac cycle; however serious ones can be fatal
Arrhythmias
The phenomenon of reentry, which results from premature stimulation of previously activated myocardial fibers can cause
Tachyarrhythmias
Can be caused by a unidirectional block of conduction of the cardiac AP with slowed conduction through the reentry path
Reentry
In order for reentry to occur, a region of fibers within the conduction pathway must have an abnormally short
Refractatory period
Travel in proximity to the PSNS efferents along the right and left vagus nerves to the heart
Post-ganglionic SNS fibers
Dissociate from the vagal tracts and accompany the coronary blood vessels through the myocardium
SNS fibers
What do the following SNS fibers do>
- ) SNS fibers from right vagus nerve
- ) SNS fibers from left vagus nerve
- ) Increase HR
2. ) Increase contractile force of myocardium
Electrical activity of the heart is measured via the
Electrocardiogram (ECG)
An ECG is based upon the principle of
-can be mathematically represented by a vector
Electromotive force (EMF)
Divided by distinct wave segments (P, QRS, and
T) that directly reflect the electrical events occurring in specific regions of the myocardium at a given moment in time
Electrocardiograph
The ECG tracing is divided in boxes. Reading horixzontally, the boxes indicate
Time (each small box (1mm) = 0.04 seconds)
The ECG tracing is divided in boxes. Reading vertically, each 1mm box indicates
Voltage
- upward is positive
- downward is negative
The net voltage for a given waveform is simply the difference between
Upward and downward deflection
Upward deflections within the ECG represent a depolarization wave moving toward a
Positive eletrode
Downward deflections within the ECG represent a depolarization wave moving
Away from positive electrode
Repolarization waves moving away from a positive
electrode will also induce
Upward deflections
Thus, in the normal heart, the deflections of R and T waves in a given lead should be
Matched
