5000 Myocyte Structure and Function

membrane:

1. ______ of ________ (aka plasma membrane) where hydro_____ heads are outside and hydro______ tails are inside

2. this orientation is so _______ ________ cannot get in (the cell cannot get _______ unless they go through ______)

3. contains ____-specific pumps/channels

4. has _______ for signaling molecules

5. has _______ which are _______ proteins that connect cells to other cells/CT

bilayer; phospholipids; philic; phobic; charged molecules; excited; channels; ion; receptors; integrins; anchoring

interior:

1. _______ = genetic blueprint

2. ________ network

3. ____/____ = protein/lipid ______ & ____ storage

4. _____ = store/alter/pack secretory products

5. ________ = protein synthesis

6. ________ = degradation of organelles/pathogens

nucleus; mitochondrial; ER/SR; synthesis; Ca++; Golgi; ribosomes; lysosomes

why is cellular membrane important? because the new ablation technology of ____ uses ___________ to cause cellular death; it is an ultra-rapid _______ ______ above a tissue cell’s specific ______ ________ that destabilizes the membrane by forming ______ ______ that leads to _______; cardiac cells are more sensitive to it BC: 1) high ______ ______? 2) lower ______ threshold?

PFA; electroporation; electrical pulse; electrical threshold; nanoscale pores; apoptosis; metabolic activity; damage

myocyte morphology:

1. ___-___ billion in average human heart

2. specialized for ______ _____ generating contractions

3. shape = _______/________

4. organelles are _______ to other cells, but there are ___ or ___ nuclei and the mitochondria are up to ___% of cell volume

5. cytoplasmic space is mainly occupied by _______ _________ (have a ________ appearance) in a filament/branching lattice = ________

6. interconnections = _________ ____ that lead to syncytium

2-3; rhythmic force; irregular/branching; similar; 1 or 2; 35; contractile proteins; striated; myofibrils; intercalated discs

mitochondrial density and formation:

1. fast twitch glycolytic skeletal muscle: ___% with _____ arrangement

2. slow twitch oxidative skeletal muscle: ___-___% with _____ arrangement

3. myocyte: ___% with ______ arrangement

5; thin; 5-12; webbed; 35; dense

intercalated discs consist of 2 things…

gap junctions and desmosomes

gap junctions:

1. _______ pores

2. use _______ that is a hexagonal protein structure

3. it is a ___-resistance pathway that allows transmission of ___ ______ (which allows for _______)

4. can ______ in pathological conditions

5. there are ________ in the AVN which is why it takes _______ for a signal to go through there

6. these connect cells ________

aqueous; connexons; low; ion currents; syncytium; close; fewer; longer; electrically

desmosomes:

1. ________ hold adjacent myocytes together during ________

2. _________ (protein filaments) extend from _______ (thick areas of ________) of adjacent cells and ________ them

3. contain __________ 1 & 2 as part of the ______

4. allows transmission of _____ across the myocardium

5. connects cells ________

6. _____ can impact desmosomes

physically; contraction; cadherins; plaque; sarcoplasm; interdigitate; desmoplakin; plaque; force; mechanically; ARVC

ion channels:

1. cell is _______ at rest (___ in, ___ out, ___ out)

2. ________ and _______ gradient maintain charge

3. cell is permeable to ___; it wants out due to the _______ gradient, but it wants in because of the _______ gradient, so it balances

4. ___________ _________ inhibits SERCA pumps

5. NXC exchanges ___ Na+ ___ and ___ Ca++ ___

6. Na+/K+ pumps exchange ___ Na+ ___ and ___ K+ ___

negative; K+; Na+; Ca+; concentration and electrical; K+; concentration; electrical; dephosphorylated phospholamban; 3; in; 1; out; 3; out; 2; in

RMP is when…

electrical and concentration gradients of K+ are equal across membrane

SERCA = ___-___% of Ca++ uptake

NCX = ___-___% of Ca++ uptake

Ca++ ATPase = ___% of Ca++ uptake

70-75; 20-25; 1

_____________ ______________ inhibits SERCA

dephosphorylated phospholamban

movement depends on:

1. ________ gradient

2. ________ _________ (electrical forces/charges)

3. ____ (____) state for those that require it

4. ________ factors like SNS/PNS

5. ________ (like ______ or ______)

6. _____

7. and ________

concentration; transmembrane potential; ATP (energy); extrinsic; gating; voltage or receptor; meds; disease

ischemia means cell cannot produce ____ so then ________ do not work and cell can’t control _________ activity and it leads to a fatal __________

ATP; channels; electrical; arrhythmia

3 passive ion channels… (they use _______ ________ to move ions)

Na+, K+, Ca++; concentration gradient

1 passive cotransport… (they use ________ _______ to move _______ ions at the same time)

NCX; concentration gradient; multiple

2 active transport… (they use ____ to move ions)

Na+/K+ pumps and Ca++ ATPase pumps; ATP

why is ion movement important?

1. the impact of ______ on certain ______

2. when diseases are _________

drugs; pumps; channelopathies

drugs:

1. class 1 works on phase ___

2. class 2 works on phase ___

3. class 3 works on phase ___

4. class 4 works on phase ___

0; 4; 3; 2

fast Na+ channels (1-2 ms):

1. _______ gated

2. impact phase ___ of _______

slow Na+ channels (funny):

1. ______ and ______ gated

2. contributes to phase ___ in ________ cells

voltage; 0; myocytes; voltage and receptor; 4; pacemaker

L-type Ca++ channels:

1. _______ gated

2. ____ inward, ___-lasting current; impact phase ___ of ________ and phases ___ and ___ of ________ cells

T-type Ca++ channels:

1. _______ gated

2. _______ current; contributes to phase ___ in ________ cells

voltage; slow; long; 2; myocytes; 4 and 0; pacemaker; voltage; transient; 4; pacemaker

inward rectifier K+ channels:

1. _______ gated

2. contributes to late phase ___ _________; maintains ________ potential in phase ___; closes with ________

transient outward K+ channels:

1. _______ gated

2. contributes to phase ___ in ________

rapid delayed rectifier K+ channels:

1. _______ gated

2. phase ___ _________

slow delayed rectifier K+ channels:

1. _______ gated

2. phase ___ _________

ATP-sensitive K+ channels:

1. ________ gated

2. inhibited by ___; opens when ___ ______ during cellular hypoxia

Ach-activated K+ channels:

1. ________ gated

2. activated by ___ and ______; gi-protein coupled; ______ SA nodal firing

Ca++ activated K+ channels:

1. ________ gated

2. activated by high ________ Ca++; accelerates _________

voltage; 3 repolarization; negative; 4; depolarization; voltage; 1; myocytes; voltage; 3 repolarization; voltage; 3; repolarization; receptor; ATP; ATP decreases; receptor; Ach and adenosine; slows; receptor; cytosolic; repolarization

think of rectifier channels as ________ the threshold

correcting

ion channel shorthand:

1. fast Na+ = _____

2. slow Na+ = _____

3. L-type Ca++ = _____

4. T-type Ca++ = _____

5. inward rectifier K+ = _____

6. transient outwards K+ = _____

7. rapid delayed rectifier K+ = _____

8. slow delayed rectifier K+ = _____

9. ATP-sensitive K+ = _____

10. Ach-activated K+ = _____

11. Ca++-activated K+ = _____

INa; If; ICa-L; ICa-T; IK1; Ito; IKr; IKs; IK, ATP; IK, Ach; IK, Ca

MYOCYTES:

phase 0 channels = …

phase 1 channels = …

phase 2 channels = …

phase 3 channels = …

phase 4 channels = …

1. 0 = INa

2. 1 = Ito

3. 2 = ICa-L and Ito

4. 3 = IKr, IKs, IK1

5. 4 = IK1

PACEMAKER CELLS:

phase 0 channels = …

phase 3 channels = …

phase 4 channels = …

1. 0 = ICa-L

2. 3 = IKr, IKs, IK1

3. 4 = If and ICa-T

resting membrane potential is calculated with the ______ ______ equilibrium potential

Nernst potential

Excitation of ECC PM cells

Phase 4:

1. it is the ________ RMP

2. ___ channels are responsible for pacemaker current (aka ______ channels)

3. _____ ___ _____ (different than the channels in non-PM cells) create the higher excitability

4. ___-type ___ _______ (____) - transient, open briefly at -50 mV

5. reduced ________ _________ ___ ______ (____ and ____)

Phase 0:

1. around 40 mV, voltage-gated slow ___-type ___ ______ (____) and some ___

Phase 3:

1. positive MP opens voltage gated _______ ________ ___ _______ channels (____ & ____)

unstable; I_f; funny; slow Na+ influx; T-type Ca++ influx; (I_ca-T; delayed rectifier K+ efflux (I_ks and I_kr); L-type Ca++ influx; I_ca-L; I_ca-T; delayed rectifier K+ efflux; I_ks & I_Kr

Positive chronotropic response:

1. ____ (SNS) or ____ (adrenal medulla) binds to ____ adrenergic receptors that stimulates ___ ________ that activate ________ _________ that causes the hydrolysis of ATP to _______ cAMP which increases protein _______ ___ which increases _____________ of different channels causing more of them to ______

2. phase 4 = increased ___ channels open and earlier ___ and ___ channels open

3. phase 0 = increased ___ channels open

4. phase 3 = increased ___/___ _______ activity

NE; Ep; B1; G proteins; adenylyl cyclase; increase; kinase A; phosphorylation; open; If; ICa-L and ICa-T; ICa-L; Na+/K+ ATPase

negative chronotropic response:

1. ____ (PNS-vagal) binds to ____ receptors that causes _________ ___ proteins (Gi) that inhibits _______ ________ which ________ cAMP and produces less protein ________ ___ so there is less __________ of channels

2. phase 4 = decreased ___ channels opening

3. phase 0 = decreased ___ channels opening

4. phase 3 = decreased ___/___ ________ activity

5. ____ also binds to special channels ____ that lowers the RMP by increasing ___ ______, making the cell less _______

Ach; M2; inhibitory G; adenylyl cyclase; decreases; kinase A; phosphorylation; If; ICa-L; Na+/K+ ATPase; Ach; IK, Ach; K+ efflux; excitable

nonneural increasing rate factors:

1. ________ stimulation

2. muscarinic receptor _________

3. beta-adrenergic _________

4. circulating __________

5. ____kalemia (there is _____ K+ in the blood, so K+ _____ the cell more quickly allowing faster _________)

sympathetic; antagonist; agonist; catecholamines; hypo; less; leaves; repolarization

nonneural decreasing rate factors:

1. __________ stimulation

2. muscarinic receptor ________

3. beta-_________

4. __________/___________ (because the pumps _____ _____)

5. ____kalemia (there is _____ K+ in the blood, so K+ does not ____ the cell, causing _______ repolarization)

parasympathetic; agonist; blockers; ischemia/hypoxia; don’t work; hyper; more; leave; slower

Contractile myocyte action potential:

1. phase 0 = ____ channels (___flux) are open for ___-___ms then inactivate; also decreased ____ _______ via the ____ channels

2. phase 1 = ____ channels open causing a ________ ___ _______ and slightly _________ the cell

3. phase 2 = ____ channels also open (at around ___mV; _____-gated) causing ___ ______ that matches the ___ ________ caused by the ___ and ___ channels (_______ ________ channels)

4. phase 3 = closing of the ___ channels and further opening of the ________ rectifier ____ and ____ (___ ________) and ________ rectifier ____

5. phase 4 = return of RMP by ___ _______ using the ___ channels and ___/___ ATPase pumps (___ ____ out and ___ ____ in); also does ___ removal to allow for relaxation

INa; in; 1-2; K+ efflux; IK1; Ito; transient K+ efflux; repolarizing; ICa-L; -40; voltage; Ca++ influx; K+ efflux; IKr and IKs; delayed rectifier; ICa-L; delayed; IKr and IKs; K+ efflux; inward; IK1; K+ efflux; IK1; Na+/K+; 3 Na+; 2 K+; Ca++

3 other ways to remove Ca++

NCX (3 to 1), SERCA, and Ca++ ATPase pumps

differences in AP in cardiac muscle cell:

1. phase 1 = atrial muscle have _________ delayed rectifier current (____) that is not in ventricle

2. AP times: nodes = ___ms; V = ___ms; Purkinje = ___ms

3. phase 2 = differences primarily due to the different ________ of different ____ ________ (or ___ channel _____)

ultrarapid; IKur; 150; 250; 300; distributions; ion channels; Ca++; isoforms

refractoriness depends on ________ of ___ channels that have recovered from the _________ state and are capable of ________

1. _________ RP = unexcitable to new stimulus 

2. _________ RP = stimulus can produce ______ AP but not strong enough to _______

3. _________ RP = stimulus can trigger a _________ AP, but rate of rise is _____

4. __________ period = ____ than normal stimulus can trigger AP

percentage; Na+; inactive; reopening; absolute; effective; local; propagate; relative; conducted; less; supranormal; less

class 1 drugs effect ____ channels

class 2 drugs effect ____ channels

class 3 drugs effect ____ and ____ channels

class 4 drugs effect ____ channels

INa; IK1; IKr and IKs; ICa-L

not all cardiomyocytes are created _______

equal

myocyte microscopic view:

1. myocyte contains _______ called ________ that run parallel to each other along the long axis of the cell

2. ________ fill most of the _______ space (similar to SM) and are made up of _______ of _______ (the smallest functional unit of muscle, the ______ element)

bundles; myofibrils; myofibrils; cytoplasmic; series of sarcomeres; contractile

sarcomere:

1. ___ ______ to ___ _______

2. about ___-___ micrometers in human hearts

3. about ___-___ micrometers in human skeletal muscle

Z disc to Z disc; 1.6-2.2; 1.3-3.5

T-tubules:

1. deep _________ __________ of the __________ at each Z disc

2. open to the ____

3. permit exchange between ____ and ________ compartment

4. transmit ___ deep into the myocyte

5. structurally and functionally connected to ____

6. heart has less developed ___ but T-tubules have ___x diameter and ___x volume than SM (it cannot _____ as much, but it can ______ ___ more; that means it relies on _______ ____)

7. ____________ Ca++ channels (____ channels) release ______ Ca++

8. store large quantities of __________ like calsequestrin and parvalbumin

transverse invaginations; sarcolemma; ECF; intra and extracellular; AP; SR; SR; 5; 25; store; bring in; external Ca++; dyhydropyridine; ICa-L; trigger; mucopolysaccharides

sarcoplasmic reticulum:

1. they surround the _________

2. account for ___% of cell volume

3. regulate and store _________ ___

4. ________ SR are close to T-tubules (____ structure) and has _________ receptors for Ca++ release channels

5. ________ SR are sac-like expansions near the ___ band that hold a ______ concentration of Ca++

6. ________ SR run parallel with T-tubules (________) and contain ______ pumps that removes ___% of the Ca++ from SR

myofibrils; 5; intracellular Ca++; junctional; diad; ryanodine; corbular; I; high; network; transverse; SERCA; 75

sarcomere: _______ filaments that make up the sarcomere account for ___% of cell volume

contractile; 50

myosin:

1. ______ filament; ___ molecules in myosin

2. about ___ mincrometers long (operates at a ______ length than SM)

3. has ______ enzyme and the ______ ________ site on each head

4. each myosin surrounded by ________ arrangement of ______

thick; 300; 1.6; shorter; ATPase; actin binding; hexagonal; actin

actin:

1. ______ filament; contains ___ actin (the ________) and ___ actin (a ______ of ___); 2 ___ actin make the actin ________

2. tropomyosin is __________ between ___ actin strands (each associated with ___ actin molecules)

3. troponin is ___% attaches to tropomyosin at regular intervals and ___% in cytosol

4. TN-T binds to _________; TN-C binds to ___; TN-I is ________ and binds with ______

5. _____ and _____ are cardiac markers (released when myocyte _____) because their ________ are specific to cardiac tissue whereas _____ is not

thin; G; globular; F; string; G; F; molecule; interdigitated; F; 7; 90; 10'; tropomyosin; Ca++; inhibitory; actin; TN-T and TN-I; dies; isoforms; TN-C

titan:

1. _______ myosin to ___ _______

2. limits _________

3. may release a ______ signal when stretched

4. plays a role in ________ _________ (restoring ______) via ________ ________

5. involved in the _______ filament theory (when lengthened, it ______ around _____)

6. ________ propertied play role in passive mechanical properties of heart (most force produced during ________ phase of contraction)

stabilizes; Z disk; overstretching; growth; diastolic filling; force; dynamic relaxation; twisting; twists; actin; elastic; eccentric

other proteins:

1. ________ anchors actin in place

2. _____ ______ also anchors actin in place

3. ________ attaches cytoskeleton to ECM and sarcomere to sarcolemma

4. ________ is the cross that holds our cells together

nebulin; alpha actin; costamere; laminin

crossbridge:

1. a single CB shortens sarcomere only ___%

2. cardiac muscle can shorten to ___%

1; 30

during diastole, ____ is ________ and myosin head is ________; then the ___ forms and ___ and ___ are released; then the _________ occurs; then ____ is reattached; this process continues until ___ levels decrease at the end of phase ___ of the AP (this process is called _______ ________ _________)

ATP; hydrolyzed; energized; CB; Pi; ADP; powerstroke; ATP; Ca++; 2; cross bridge cycling

Ca++ induced Ca++ release:

1. AP triggers ____ channels (AKA ___________ channels) to release ______ ____ (this is the ___ in phase ___ of AP)

2. the _______ ___ alone does not increase intracellular Ca++ concentration except in local regions; most activates the release of ___ from ________ _______ on the ___ which leads to a ____ fold increase in Ca++

3. these receptors are _______-gated

4. Ca++ binds to TN-C in a __________-dependent manner

ICa-L; dihydropyridine; trigger Ca++; Ca++; 2; trigger Ca++; Ca++; ryanodine receptors; SR; 100; ligand; concentration

ECC (systole):

1. depolarization from an increased ___ _______

2. ___ channels cause a transient ___ ______

3. ____ channels release _______ ___

4. that causes ________ receptor ___ release from ___

5. plateau occurs because ___ influx = ___ and ___ efflux

6. intracellular Ca++ binds to ________ ___

7. ____ (abbreviation) has a ________ ______ and pulls _________ off of the ______ _______ site

8. ____ formation occurs with an _______ myosin head on actin

9. ____ and ___ are released

10. __________ occurs

11. a new ____ binds to myosin and is immediately _________ into ___ and ___ by the enzyme _______

12. this repeats as long as ____ remains and is called ______ ______ ______

INa influx; Ito; K+ efflux; ICa-L; trigger Ca++; ryanodine; Ca++; SR; ICa-L; IKr and IKs; troponin C; TN-C; conformational change; tropomyosin; actin binding; CB; energized; ADP and Pi; powerstroke; ATP; hydrolyzed; ADP and Pi; ATPase; Ca++; cross bridge cycling

diastole:

1. closing of ____ and opening of ___, ___, and ___ (____ ________)

2. cell _________

3. ____ is also reuptaken by ______, ____, _______pumps and the concentration _________ which causes Ca++ to release from ____ and contraction stops

4. diastole is also enhanced by ____ via _________ of ___________

ICa-L; IK1, IKr, IKs; K+ efflux; repolarizes; Ca++; SERCA; NCX; Ca++ATPase; decreases; TN-C; SNS; phosphorylation of phospholamban

cardiac inotropy:

1. resting muscle sarcomere length has an ______ ________ related to ____ formation

2. maximal force is around ___-___ micrometers

3. overlapping ___ _____ or ___ ______ limits CB formation and therefore force

4. too much _______ (like in ________ myopathies) limits force

optimal force; CB; 2.1-2.2; too much; not enough; stretch; dilated

length tension relationship with increased EDV:

1. increased RV ______ the LV output via the _______ ________ mechanism, but why?

   1. _______/________ relationship

   2. increased Ca++ _________ and __________

   3. decreased ________ _________

matches; Franck Starling; length/tension; sensitivity/availability; fiber diameter

inotropy via ICa-L influx:

1. positive: SNS, ___/___, ___ receptors, ____ stimulates ____, which _______ ATP into _____, which stimulates ___ which _________ ICa-L to increase ____ Ca++ release to increase ____ formation to increase _____

2. negative: PNS, ___, ___ receptors, ____ inhibits ____, which decreases _____ availability, which decreases ____, which decreases phosphorylation of ____ channels, which reduces ____ Ca++ release

NE/Ep; B1; Gs; AC; hydrolyzes; cAMP; pKA; phosphorylates; SR; CB; force; Ach; M1/2; Gi; AC; cAMP; pKA; ICa-L; SR

inotropy via SERCA Ca++ release:

1. positive: SNS, ___/___, ___ receptors, ____ stimulates ____, which _______ ATP into _____, which stimulates ___ which phosphorylates ____ Ca++ channels to increase ____ Ca++ release, which increases ____ formation to increase _____

2. negative: PNS, ___, ___ receptors, ____ inhibits ____, which decreases _____ availability, which decreases ____, which decreases phosphorylation of ____ channels, which reduces ____ Ca++ release

NE/Ep; B1; Gs; AC; hydrolyzes; cAMP; pKA; SR; SR; CB; force; Ach; M1/2; Gi; AC; cAMP; pKA; SR; SR

inotropy via Ca++ binding to TN-C:

1. _________ dependent, so positive inotropic is from an ________ ________; also, increased _________ seems to _________ TN-C’s affinity for Ca++ when it ________ the myocyte

2. _________/_________ decreases its affinity

concentration; increased concentration; preload; increase; stretches; hypoxia/acidosis

myosin phosphorylation Ca++ role:

1. positive: SNS, ___/___, ___ receptors, ____ stimulates ____, which _______ ATP into _____, which stimulates ___ which _________ _____ on myosin heads to increase inotropy (uncertain)

NE/Ep; B1; Gs; AC; hydrolyzes; cAMP; pKA; phosphorylates MLCK

Ca++ role in SERCA activity:

1. increasing Ca++ ____ SR by SERCA indirectly increases amount of ___ _________ by SR for __________ beat, so more force

2. _________ ______________ inhibits SERCA, so when NE/Ep binds to B1 and stimulates ___ to activate ___ to make ____, to activate ___, it ___________ ___________ and removes its __________ on SERCA to increase Ca++ _______

3. in ________ conditions, there is less _____, so SERCA cannot pump, so less ____ into SR, and less ____ for ______ ____, so less force

into; Ca++ released; subsequent; unphosphorylated phospholamban; Gs; AC; cAMP; pKA; phosphorylates phospholamban; inhibition; reuptake; hypoxic; ATP; Ca++; Ca++; subsequent beat

Ca++ role in Ca++ efflux across sarcolemma:

1. Positive: normally, ____ and _____ pumps work to prevent too _____ intracellular Ca++, so when they are inhibited, there will be an ________ amount of intracellular Ca++, so ______ can go ________ the SR and cause more force for ________ _____

2. digoxin inhibits ___/___ pumps which then causes increased intracellular ___, so the ____ pumps don’t work (because they rely on _________ ________); now there is increases intracellular ___ (because it wasn’t able to leave via the ____ pumps) that can be taken up by ___ and more force is available for _______ ____

3. hypoxia also inhibits ___/___ pumps, but because there is no ____, the ______ pumps cannot get ___ into the ___, so there is no increased ___ for the _______ ______ to have more force

NCX and Ca++ATPase; high; increased; more; inside; subsequent beat; Na+/K+; Na+; NCX; concentration gradient; Ca++; NCX; SR; subsequent beat; Na+/K+; ATP; SERCA; Ca++; SR; Ca++; subsequent beat

Lusitropy = the cell’s ability to rapidly _______ the amount of ________ ___ and to regain a ______/_______ state

Ca++ role in lusitropy:

1. Positive: SNS leads to increased ____/____ that increases phosphorylation of ______ pumps on the ___ to increase ___ _____; increased ____/____ also increases phosphorylation of ____ that inhibits ___ formation

2. Negative: if there is myocardial ________, cells are more _______ to Ca++ which can lead to Ca++ _______; some HFs can impair ______ pumps which increases _________ Ca++ and impairs relaxation; some ________ drugs increase ____ affinity of Ca++ and decreases Ca++ ______, so they increase inotropy, but decrease lusitropy

3. rapid return to resting is important for _________ _________

decrease; intracellular Ca++; resting/diastole; cAMP/pKA; SERCA; SR; Ca++ uptake; cAMP/pKA; TN-I; CB; ischemia; permeable; overload; SERCA; intracellular; inotropy; TN-C; efflux; ventricular filling

Ca++ role in hypertrophy:

1. impacts _____ ________ in the nucleus

2. ____ and ____ cause an increase in Ca++ that can lead to cardiac ________

gene expression; ET-1; AngioII; remodeling

why is Ca++ important? devices like ______ _______ _________ (CCM) that delivers a non-excitatory electrical signal during ________ refractory to increase ________ ___ that can be used for more ___ formation and therefore create more _____

MOA:

1. increases _____ channels’ ______ of Ca++

2. increases ____ pumps’ Ca++ ______

3. increases ____________ phosphorylation (allowing ______ reuptake)

4. and increases _______ activity

cardiac contractility modulation; absolute; intracellular Ca++; CB; force; ICa-L; influx; NCX; entry; phospholamban; SERCA; SERCA

first law of thermodynamics/principle of conservation of energy: energy cannot be _________ nor ________, only ________/_________ from one form to another…. that means we are all technically ______ powered:

1. sun turns into ______ E which we eat and gets turned into ______ E as AP, which then gets turned back into _______ E which is turned into _______ E, ______, and _____ when our muscles use it

created nor destroyed; transferred/transformed; solar; chemical; electrical; chemical; mechanical; heat; CO2

Fueling ECC:

1. there is ________ amounts of ATP stored in the body

2. ATP ________ turns over every ___ seconds

3. the heart consumes ___-___x its weight in ATP per day! about ___kg daily!

4. the myocardial energy reserve from ATP alone is only about ___ sec and from PCr is about ___ sec

5. we don’t ______ a lot, but we ____ a lot, so we have to ______ a lot

6. thus, we need a _______, _______ production of ATP and a TIGHT coupling of ________ and ________

minimal; hydrolysis; 10; 15-20; 6; 10; 60; store; use; make; continuous, unimpeded; production and utilization

Myocardial bioenergetics:

1. 95% of ATP is from __________ _________

2. 5% of ATP is from ________ ________ ___________

3. 60-70% of ATP hydrolysis is used for _________ process

4. 30-40% of ATP hydrolysis is used for ________, ___/___ _____, and other _____ _______

oxidative phosphorylation; substrate level phosphorylation; contractile; SERCA, Na+/K+ ATPase; ion pumps

bioenergetics:

1. ATP hydrolysis enzyme is ______; the reactants are ____ + _____ and they from the products of ____ + _____ + _______

2. PCr system uses the enzyme _______ ________; the reactants are ____ + ____ and they form the products ____ + ____

   1. the product of ____ is also used as a cardiac marker using the isoform ______; this marker means there is not enough ____ available so it is relying on other systems to make it

3. ADP system uses the enzyme ________; the reactants are ____ + ____ and they form the products ____ + ____

4. the ____ from the ____ and ____ systems is then used by ______ enzyme to create “_______”

ATPase; ATP + H2O; ADP + Pi + energy; creatine kinase; PCr + ADP; ATP + CR; CR; CR-MB; ATP; myokinase; ADP + ADP; ATP + AMP; ATP; PCr and ADP; ATPase; energy

because of limited stores, we are ALWAYS manufacturing more ___:

1. 5% is ________ ________ phosphorylation:

   1. ____/___ + ____ + ____ = ATP

2. 95% is ________ phosphorylation:

   1. ____ + ___ + ___/____ (____/____) + ____ = ATP

substrate level; CHO/ffa + ADP + Pi; oxidative; ADP + Pi + cho/FFA (NADH/FADH) + O2

Oxidative phosphorylation:

1. direct measurement of ____ is not practical, so we use ____ (______ ______ _______) which is ___ x ____

2. minimal ___/___ stored

3. there is ______ O2 stored, but what is stored is via ________; ___-facilitated O2 diffusion is still only able to produce ___-___ ms of systole

4. at rest, myocyte extracts ___-___% of O2 from blood (can be seen using ____ diff), so to get more O2, it requires more ____

5. increased ____ demand must be met by increased ____ (there is a tight coupling of ____ with coronary ___)

6. regulation of ________ ___ is the “just-in-time” delivery of _______ and ___

7. because of the tight coupling of ____ with _______ ___, the ________ density in cardiac tissue is much ______ than SM; heart has ___x more and each myocyte is intertwined by ___-___ capillaries

MVO2; RPP; rate pressure product; HR x SBP; ATP/PCr; minimal; myoglobulin; Mg; 22-34; 70-80; avO2; BF; MVO2; BF; RPP; BF; coronary BF; substrates and O2; RPP; coronary BF; capillary; higher; 10; 3-4

just-in-time BF:

1. structure = endocardial BF exclusively during ______

2. feedback control/intrinsic = when myocyte ________ increases, the vessels _________ and this results in ________ ________ to increase BF

3. feedforward control/extrinsic = SNS binds to ___ adrenergic for dilation and ___ and ___ adrenergic for constriction

4. mechano-transduction = more flow induces more ______ ______ on endothelial cells, triggering the release of ____ to increase BF

diastole; metabolism; hyperpolarize; functional hyperemia; B2; A1 and A2; shear force; NO

oxidative phosphorylation myocardium:

1. mitochondrial density:

   1. the heart has ___% of cell volume vs skeletal has ___-___% and smooth has ___-___%

   2. nodal cells have ______ and more _______ mitochondria

   3. contractile cells have ______ and ________ mitochondria

2. why are mitochondria so important? they house the ______ cycle, _____ _______, and the ____ which are all important for ____ production (responsible for ___% of production)

3. the mitochondria’s ________ is important too; ____-___ creates mitochondria in the process called ________, so more of that means more mitochondria; the process of ________ is when the ones that don’t work or are inefficient are gotten rid of

4. it is also important that the _______ inside the mito are well ________ (healthier = more and therefore better ____)

35; 3-8; 3-5; smaller; globular; networked and interfibrillar; krebs; beta oxidation; ETC; ATP; 95; efficiency; PGC-1a; biogenesis; mitophagy; cristae; developed; ETC

heart is capable of using ___ ______ of energy ________: ____, ____, ____, ____, and ______ ______; this is called _________ _________; the heart selects the most ______/_______ fuel for the situation

all classes; substrates; CHO; lipids; AAs; lactate; ketone bodies; metabolic flexibility; abundant/appropriate

heart fuel selection is based on:

1. ____ _____ effect = the ______ of substates drives its use

2. ________ regulation = ________ of an enzyme drives the ________

3. environmental impact = _______, ________, and ________

mass action; level; allosteric; biproduct; production; activity, dietary, pathology

normal healthy hearts fasted used:

1. ___% FFAs

2. ___% CHO

   1. ___% glucose

   2. ___% lactate

3. ______ AAs and ketone bodies

60; 40; 30; 10; minimal

CHO:

1. stored as ________ in the ______ and ______

2. transported as ________ after being broken down via _________

3. created for storage via __________

4. created for usage via _________

5. glucose is broken down via _________

6. we have ______ storage

7. creates ___ kcal/g

glycogen; liver and muscles; glucose; glycogenolysis; glycogenesis; gluconeogenesis; glycolysis; minimal; 4.1

fats:

1. stored as _________ in _______

2. transported as ____ (via _______) after being broken down via ________

3. for fats to be ATP, they go through ____ _______ inside the ___________

4. we have _________ storage

5. creates ____ kcal/g

triglycerides; adipocytes; FFAs; albumin; lipolysis; beta oxidation; mitochondria; abundant; 9.4

proteins:

1. broken down into ____

2. used during _________

3. creates ____ kcal/g

AAs; exercise; 4.5

carbohydrates:

1. stored as _______ (minimal in the _____, but much more in the ______ and ______)

2. glycogenolysis is the process of breaking ________ down into _______

3. transported in the ______ in the form of ________ (around 60g)

4. sarcolemma transport requires _____ and _____ (which are _______-dependent protein molecules that help glucose into cell) and _____ 1&2 (stands for _______ ________ _________ and means that glucose comes into cell with ____ which causes ____ to follow due to osmotic gradient, reducing ____ for HF patients)

glycogen; heart; liver and muscles; glycogen; glucose; blood; glucose; glut1 and glut4; insulin; SGLT; sodium glucose transport; Na++; H2O; BV

Glycolysis:

1. this is _______ ________ phosphorylation, meaning it is _______ and does not use ___

2. this is turning 1 _______ (___ carbon unit) into 2 ________ molecules (___ carbon units)

3. to keep/trap glucose in the cell, the enzyme ________ uses ___ to ________ it turning it into ____

4. stored _______ does not require ___ to phosphorylate, turn it into ____ and trap it in the cell

5. then the enzyme __________ (___) uses ___ to ________ G6P (this is the ____ _______ step)

6. there are ___ ATPs produced from each pyruvate, so gross ATP is ___

7. if glucose is substrate, there are ___ ATP used, so net is ___

8. if glycogen is substrate, there is ___ ATP used, so net is ___

substrate level; anaerobic; O2; glucose; 6; pyruvate; 3; hexokinase; ATP; phosphorylate; G6P; glycogen; ATP; G6P; phosphofructokinase (PFK); ATP; phosphorylate; rate limiting; 2; 4; 2; 2; 1; 3

glycogenolysis of stored glycogen influences:

1. ___, ___, and ___ all increase its activity

2. ___, ___, and _______ all decrease its activity

3. this makes sense because if we do not have ___, then we need to make it; if we do have ___, then we do not need to make it

4. also makes sense because if _______ is high, that means ___ is high and we will use ___ as energy instead of breaking down our energy ______

5. this is an example of _________ modulation because the ________ influence the production

Pi, ADP, and AMP; G6P; ATP; insulin; ATP; ATP; insulin; BG; BG; stores; allosteric; biproducts

PFK influences:

1. ___, ___, and ___ all increase its activity

2. ___, ______, and ___ ions all decrease its activity

3. this makes sense because if we do not have ___, then we need to make it; if we do have ___, then we do not need to make it

4. this also makes sense because ____/____ exchange ___ ions for energy, so if there is a lot, that means we do not need to keep making it; also, if ___ ions are high, then the body is _____, so we do not need to make a ______ _______ precursor

Pi, ADP, and AMP; ATP, citrate, and H+; ATP; ATP; NADH/FADH; H+; H+’ acidic; pyruvic acid

pyruvate then enters the _______ ________:

1. __________ ____________ (____) enzyme is what combines ____ with ___ ions to make _____

2. then the product becomes ____

3. its activity is increased by ____, ___, and ______

4. its activity is decreased by ___, ____, and _____

5. further in the cycle in steps 5/6, ___, ___, and ___ increase activity and ___ decreases activity

Krebs cycle; pyruvate dehydrogenase; PDH; NAD+; H+; NADH; ACoA; ADP, Ca++, and insulin; ATP, ACoA, and citrate; ADP, Pi, and Ca++; ATP

Krebs cycle:

1. FFA through _____ _______ also enters when it is _____ (this is the ____ _______ step)

2. the products per ____ are:

   1. ___ ___

   2. ___ ____

   3. and ___ ____

beta oxidation; ACoA; rate limiting; ACoA; 1 ATP, 3 NADH, 1 FADH

ETC:

1. FADH/NADH create an ________ gradient that drives _______ _______ of ATP therefore it is called ___________ gradient

2. it needs ___ to accept ___ to create ___ (and ___ + ___ = ____)

3. NADH has a ______ gradient than FADH, so it results in ___ ATP but FADH only results in ___ ATP

electrical; chemical phosphorylation; electrochemical; O2; e-; ATP; O2 + H+ = H2O; larger; 2.5; 1.5

lipid metabolism:

1. fats stored as __________ in mostly ________

2. broken down via process called _________ (____)

3. this process is stimulated by _____ and inhibited by ________

4. fats are transported as ____ by molecules of _______; they can also be transported as _________ with VLDL or chylomicron

5. sarcolemma transport is heavily dependent on blood __________; 70% of uptake into cell is done by _____

6. transport into the mito is by ________/____

7. ultimately the process that results in ATP is ______ _________

triglycerides; adipocytes; lipolysis (LPL); SNS; insulin; FFAs; albumin; triglycerides; concentration; CD36; carnitine/CPT; beta oxidation

triglycerides:

1. composed of a ________ backbone and 3 _____ _______

2. those 3 are long ________ chains

3. each _____ of _______ become ______ that then enters the _______ cycle to form ATP, NADH, and FADH

glycerol; fatty acids; carbon; pair; carbons; ACoA; Krebs

each carbon pair is a ___-carbon molecule, so ________ agents take the ___ ion (and take it to the ____) to convert it into ______; this enters the ______ cycle to produce ___ ATP, ___ NADH, and ___ FADH

2; reducing; H+; ETC; ACoA; Krebs; 1; 3; 1

the last carbon pair does not need to be _______ ________ of the tail, so it goes straight into the _______ cycle to form ___ ATP, ___ NADH, and ___ FADH

broken off; Krebs; 1; 3; 1

CHO vs Lipids:

1. glycolysis:

   1. creates ___ ATP and ___ NADH (which is then ___ ATP)

   2. PA converts to ACoA and results in ___ NADH (which is then ___ ATP)

   3. 2 ACoA enters the Krebs cycle twice to create ___ ATP, ___ NADH (which is then ___ ATP), and ___ FADH (which is then ___ ATP)

   4. GROSS ATP = ___

2. beta oxidation:

   1. FFA each pair before the final pair results in ___ ATP from ___ FADH x 1.5, ___ NADH x 2.5, and ___ ATP

   2. the final pair only has ___ ATP from ___ FADH x 1.5, ___ NADH x 2.5, and ___ ATP

   3. GROSS ATP = _____ than CHO

4; 2; 5; 2; 5; 2; 6; 15; 2; 3; 34; 14; 2; 4; 1; more

bottom line: out best form of energy storage is _____

fats

fueling ECBC in nonischemic myocardium:

1. when there is a buildup of _______ _______, the heart can use it (SM cannot)

2. it converts it into ________ ________, then ________ (the first step in the ______ cycle)

3. this then inhibits transport of _____ into mito by blocking ____

4. this is a good thing because the heart is able to use whatever is _______ ___; when _______ _______ builds up, it uses that and inhibits the use of ____

5. therefore: ________ competes with ____ for mitochondrial oxidation

lactic acid; pyruvic acid; citrate; Krebs; FFA; CPT; building up; lactic acid; FFA; lactate; FFA

FFA competing with LA for mito oxidation:

1. when myocyte concentration of FFA _________, it inhibits _________ receptors ______ ___ transport

2. if there is more ____ available, it is going to use that instead and BLOCK the use of _______ via inhibiting ________ receptors _______ ___ transport

3. ALSO, if you have just eaten a meal, ________ is going to increase, so then ________ increases (which then inhibits ______ of ____ to increase the use of ________)

4. again, the heart is going to use what it has ______ of

increases; insulin; Glut 4; FFA; glucose; insulin; Glut 4; glucose; insulin; lipolysis of fats; glucose; more

glucose to G6P is regulated by ________ enzyme

hexokinase

glycogen to G6P is regulated by _____ enzyme; process inhibited by ____, _____, and ________; process stimulated by ___, ____, and ____

GP; G6P; ATP; insulin; Pi, ADP, AMP

G6P to 3PG is regulated by _____ enzyme; process is inhibited by ____, ______, and ___ ions; process is stimulated by ____, ____, and ____

PFK; ATP; citrate; H+; Pi; ADP; AMP

PA to LA is regulated by _____ enzyme

LDH

PA to ACoA is regulated by _____ enzyme; process is inhibited by ____, ______, and _______; process is stimulated by ____, ____ ions, and _______

PDH; ATP; ACoA; citrate; ADP; Ca++; insulin

ACoA to Citrate is regulated by _______ ________ enzyme

citrate synthase

ACoA to end of beta oxidation is regulated by __________ _________ ___________ (____); process inhibited by ____; process is stimulated by ___, ____, and ____ ions

isocitrate oxalosuccinate dehydrogenase (ISD); ATP; Pi; ADP; Ca++

Glut 4/1 are inhibited by increased myocyte _____ concentration

FFA