Cardiovascular Systems Physiology and Pathophysiology II Flashcards by Joel Glotfelty

Cardiac APs are initiated within nodal tissues and are conducted through the bundle branches to the

Myocardium

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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

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To begin one pacemaker cycle, a gradual depolarization is enabled by

Inward Ca2+ and Na+ and outward K+

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During the gradual depolarization, the membrane potential creeps upward, becoming less negative and reaching around

-55 mV

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What happens at around -55 mV?

T-type Ca2+ channels are increasingly activated

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The increasing activation of T-type Ca2+ channels in a pacemaker potential produces a rapid upstroke in

Action potential

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HCN and Ca2+ channels are inactivated, shutting down If, and thus allowing repolarization via K+ efflux at about

0 mV

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Repolarization leads to a brief period of hyperpolarization which is necessary to reactivate

HCN channels

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In a cardiomycete depolarization-repolarization plateau potential (different from pacemaker potential) phase 0 is dependent upon

Na+ influx

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The rapid, Na+ dependent depolarization of cardiac muscle is followed by phase 1, which is a

Transient K+ dependent repolarization

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On the sarcolemma, the Na+ dependent AP also activates

Votage gated- Ca2+ channels (Type L)

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Increased intracellular Ca2+ stimulates the release of
Ca2+ via activation of

-called calcium induced calcium release

Ryanodine receptors within SR

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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

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To complete the cycle of cardiac muscle AP, phase 2 is followed by phase 3 which is a

Rapid K+ dependent repolarization

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Phase 4 of the plateau potential is a

Slight efflux of K+

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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)

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Because of this complex triad motif, the fundamental activation of type L channels is dependent upon the

Na+ induced AP

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Also, the L type Ca2+ channel activity is modulated by

Catecholamines and ACh

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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

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This signal transduction pathway activates L channels; thus, promoting

Ca2+ influx

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Also facilitate L channel activation but activation of this receptor can also induce lusitropy

B2 receptors

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Increased rate of relaxation that is medicated by mobilization of Gi protein dependent signaling

Lusitropy

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An increase in the dominance of cardiac B2 activity plays a role in the pathogenesis of certain forms of

Heart failure

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Activated in the presence of elevated sacoplasmic Ca2+ concentrations

Troponin C

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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

1. ) Activation of type L channels 2. ) Phospholamban is phosphorylated by PKA 3. ) 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: 1. ) Activated by? 2. ) Suppressed by?

1. ) 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?

1. ) 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

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> 1. ) SNS fibers from right vagus nerve 2. ) SNS fibers from left vagus nerve

1. ) 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