Klabunde 1

Question 1

Resting membrane ventricular myocyte ______: Resting membrane potential (Em) is determined by:

Answer 1

-90mV concentrations of +/- ions across the cell membrane electric gradient relative permeability of cell membrane to ions ionic pumps

Question 2

What main pump maintains ionic gradient:

Answer 2

What main pump maintains ionic gradient: Electrogenic : 3 Na out for every 2 K in, creating the negative potential w/in the cell

Question 3

Cardiac tissue hypoxia and cardiac glycosides (ie: digoxin) do what to Na-K-ATPase pumps, causing RMP to become ______:

Answer 3

inhibited Na-K-ATPase RMP is more positive (partially depolarized)

Question 4

Phase 0 Phase 1 Phase 2 Phase 3 Phase 4

Answer 4

Phase 0 Depolarization – Fast Na Phase 1 Transient outward K Phase 2 Plateau – L-type Ca Phase 3 Delayed rectif. Ikr (K in or out?) OUT Phase 4 Inward rectif. Ikr (K in)

Question 5

Refractory period Effective (absolute) refractory period phases: Why? Relative refractory period

Answer 5

During phase 0, 1, 2, and part of 3, that cell is unexcitable h-gates are still closed At the end of ERP (end of phase 3) Suprathreshhold depolarization required to stimulate AP Not all the Na channels have recovered to resting state based on Em When activated: decreased phase 0 slope and lower amplitude

Question 6

Phase 0 Phase 3 Phase 4

Answer 6

L-type Ca Delayed rectif. K If funny channels

Question 7

Non-nodal cell RMP determined by:

Answer 7

K concentrations (slow leak out) K electric gradient (K+ drawn to –ve intracell.) relatively permeability memb. to K (not Na+ or Ca++) ionic pumps (NA/K ATPase, delayed Ikr)

Question 8

RMP nodal cell Threshold

Answer 8

-64 -40

Question 9

RMP non-nodal: Threshold potential ______: Depolarizes to ______mV:

Answer 9

-90 -70mV +30mV

Question 10

Norepi binds to ____ receptor: B1 coupled to ____: stimulatory G protein (Gs): Gs activates _____ second messenger: cAMP act via:

Answer 10

B1 stimulatory G protein (Gs): adenylates cyclate increasing cAMP

1. increases slow Na “pacemaker current” If “funny current”
2. earlier opening of L-type Ca (phase 4)
3. Shorter repolarization is also shortened

Question 11

AcH binds to ____ receptor: M2 coupled to ____: Gi inhibits _____ second messenger: Decreased cAMP act via:

Answer 11

M2 inhibitory G protein (Gi): adenylates cyclate decreasing cAMP

1. inhibiting slow Na “pacemaker current” If “funny current”
2. Activates KAcH channels which hyperpolarize cells

Question 12

…. So we went from nodal vs non-nodal AP (phases), RMP, threshold potential, and regulation (ANS and SNS) how does AP conduct cell-to-cell: how does this differ from vascuar myocytes: how does this AP result in the heart contracting

Answer 12

gap junctions located at intercalated discs syncytium

2. non-conducting connective tissue separates/stalls AP
3. slows conduction to 0.05m/s allows atrial contraction

Question 13

Arrhythmias are generated via 3 mechanisms:

Answer 13

Abnormal automaticity

Triggered activity (EAD, DAD)

Reentry – conduction pathway prematurely stimulated by prev.AP

Question 14

Abnormal automaticity, Effects which phase of AP:

Answer 14

phase 0 i.e. blocked by drugs (digitalis) i.e. inactivated by depolarization secondary to hypoxia Depresses slope, “fast response” converted to “slow response”

Question 15

2. Triggered activity EAD (early afterdepolarization) end of phase ____: DAD (delayed afterdepolarization) end phase ____:

Answer 15

Phase 3 – Na channels still blocked, Ca++ carries depolarizing current

Phase 3/start phase 4 – elevations in intracellular Ca++ secondary to ischemia or excess catecholamines

Question 16

Klabunde 3:

Structure myocyte vs smooth m

Excitation-contraction coupling myocyte vs smooth m

More second messengers

Answer 16

Draw a single sarcomere and label 4 parts: Draw a tropomysosin complex (myosin, actin, tropomyosn and Tn-T/I/C): Draw a tropomyosin complex w. (myosin, actin, tropomyosin and Tn-T/I/C):

Question 17

Basic contractile unit Consists of 4 components:

Answer 17

Sarcomere actin (thin filament) myosin (thick filament) titin tropomyosin/tropomyosin complex

Question 18

Sarcomere turns into: ___ turns into: ____ turns into: myocytes with ____ discs

Answer 18

myofilament turns into: myofibril turns into: myocytes with intercalated discs

Question 19

Excitation-contraction coupling myocyte vs smooth m Describe the 5 key steps: 1.

2. L-type channel is what type of channel and what phase:

3.

4.

5.

Answer 19

1. AP travels down T-tubule
2. Voltage-sensitive dihydropyridine receptors (L-type calcium channels) open to permit calcium entry during phase ____ (phase 2)
3. Ca influx triggers a subsequent release of Ca stored in SR through calcium-release channels: “ryanodine receptors”

4 Ca binds to TN-C conformational change, exposes a site on actin, binds myosin ATPase on myosin head, ATP hydrolysis that supplies energy “ratcheting” actin and myosin filaments slide/shorten, ATP hydrolysis for Ca release end of phase 2

5. calcium entry into the cell slows and calcium is sequestered by the SR by an ATP-dependent calcium pump (SERCA, sarco-endoplasmic reticulum calcium-ATPase)

Question 20

describe ratcheting and sliding-filament theroy

Answer 20

-Ca binds to TN-C attached to tropomyosin -conformational change, exposes a site on actin, binds myosin ATPase on myosin head -ATP hydrolysis that supplies energy “ratcheting” actin and myosin filaments slide/shorten -ATP hydrolysis for Ca release end of phase 2 -continues to ratchet as long as Ca concentration is high

Question 21

PDE3i MoA: cardiac myocyte: vascular smooth m.:

Answer 21

PDE3i prevents degradation of PDE3 increasing cAMP (similar to B2 stimulation)

Cardiac myocyte: = increased cAMP = increased PKA (RyR > release Ca++, phosphorylates phospholamban = > SR SERCA uptake, enhances Ca++ binding to TN-C)

Vascular smooth m.: = increased cAMP = decreased MLCK (myosin light chain kinase) = smooth muscle relaxation

Question 22

RyR release NE Gs vs Gq:

Answer 22

Gs - cAMP - PKA

Gq - IP3 - PIP2 = > Ca++ release

Question 23

Lusitropy what enhances lusitropy:

Answer 23

< Ca++ allows relaxation -permiting troponin-tropomyosin to resume resting conformation

phosphorylation of phospholamban - enhanced SERCA channel ischemia = Ca overload - impaired relaxation

Question 24

Smooth muscle cells: invaginations called ____, rather than T-tubules: actin and myosin form ____, rather than z-lines: connected by:

Answer 24

calveolae - >SA dense bodies gap junctions

Question 25

smooth m AP vs. cardiac myocyte AP:

Answer 25

partially contracted state b/c of adrenergic tone

1. AP, Ca enters via L-type
2. Ca released SR
3. Ca + CALMODULIN activate MLCK
4. MLCK + ATP phosphorylates myosin = contraction

Question 26

CALMODULIN:

MLCK

MoA cAMP on MLCK

Answer 26

Ca + CALMODULIN activate MLCK

MLCK + ATP phosphorylates myosin = contraction

inhibits MLCK .:. causes relaxation

Question 27

smooth m.:

Gq binds:

causes:

Gs:

causes:

NO does what:

Answer 27

Gq - NE, AII, ET-1,

Gq - IP-3 - protein kinase C -

>Ca CONTRACTION

Gs - NE, adenosine, PGI2

Gs - cAMP - Decreases MLCK = VASODILATION

NO - > cGMP - Decreases MLCK = VASODILATION

Question 28

NO MoA vasodilation:

ET-1 MoA vasoconstriction:

Answer 28

cGMP - inhib MLCK = vasodilate

Gq PIP2 - IP3 PK-C - >Ca = vasoconstrict

Question 29

Wigger’s diagram:

Phase 1:

Answer 29

Atrial systole: A-V Valves Open; Semilunar Valves Closed

Question 30

Phase 2 -

Phase 3 -

Phase 4 -

Phase 5 -

Phase 6 -

Phase 7 -

Answer 30

Isovolumetric Contraction

Rapid Ejection

Reduced Ejection

Isovolumetric Relaxation

Rapid Filling

Reduced Filling

Question 31

Draw wigger’s diagram

Answer 31

Question 32

CO - what is more imortant HR or SV?

Answer 32

HR - can increase CO 100-200%

SV increase <50%