Cardiovascular 1

Question 1

Where is Ca2+ stored in higher concentrations?

Answer 1

intracellular stores such as ER/SR and mitochondria

Question 2

What are the 3 ways in which cytoplasmic Ca2+ levels are regulated?

Answer 2

a) Ca2+ entry mechanisms
b) Ca2+ extrusion mechanisms
c) Ca2+ exchange between ER/SR and cytosol

Question 3

What are the 3 Ca entry mechanisms?

Answer 3

1) voltage-gated Ca channels
2) ligand-gated Ca channels
3) store-operated Ca channels

Question 4

What is the mechanism of voltage gated Ca2+ channels?

Answer 4

open when cell is depolarized

Question 5

What are the different types of voltage gated Ca channels?

Answer 5

N and P = neuronal (involve NT release)
L = heart and smooth muscle

Question 6

Which drugs inhibit voltage gated Ca channels?

Answer 6

• VERAPAMIL
• DILTIAZEM
• DIHYDROPYRIDINES (DHPs), e.g. NIFEDIPINE

Question 7

Which drug is used to treat hypertension? What is the mechanism?

Answer 7

DIHYDROPYRIDINES –> inhibit voltage-gated Ca channels

Question 8

Which drug is used to treat angina and supraventricular arrhythmias?

Answer 8

VERAPAMIL and DILTIAZEM –> inhibit voltage-gated Ca channels

Question 9

What is the mechanism of ligand-gated Ca channels?

Answer 9

opened by NTs or other agoinsts

Question 10

Which ligand-gated channel in neurons is highly permeable to Ca2+?

Answer 10

NMDA glutamate channel

Question 11

Which ligand-gated channels are considered to be the only true ligand-gated ion channel in smooth muscle?

Answer 11

ATP-gated P2X channels

Question 12

What is the mechanism of store operated Ca channels (SOC)?

Answer 12

key: Ca2+ -release-activated Ca2+ (CRAC) channel

• intracellular stores depleted –> STIM1 accumulate at locations where ER is juxtaposed to the plasma membrane –> physical interaction opens CRAC channels

Question 13

What are the 3 Ca extrusion mechanisms?

Answer 13

1) plasma membrane pump (PMCA)
2) SERCA pump
3) Na-Ca exchange (NCX)

Question 14

What is the mechanisms of PMCA?

Answer 14

pump cytoplasmic Ca2+ out of the cell

Question 15

What is the mechanisms of SERCA pump?

Answer 15

pump cytoplasmic Ca2 into ER/SR

Question 16

Which drug blocks SERCA pumps?

Answer 16

THAPSIGARGIN

Question 17

What is the mechanism of the NCX?

Answer 17

• high Na out, low Na in –> chemical gradient energy used to transport Ca2+ out
• 3 Na in, 1 Ca out
• electrogenic –> depolarization by net inward movement of positive charged

Question 18

Explain reverse-mode NCX activity.

Answer 18

reduce Na gradient (inwards) –> intracellular Ca accumulation

Question 19

What are the 2 mechanisms of Ca+ exchange between ER/SR and cytosol?

Answer 19

1) inositol triphosphate (IP3) receptor
2) ryanodine receptor channel (RyR)

Question 20

What is the mechanisms of the IP3 receptor?

Answer 20

• activated by IP3
• Gq –> elevate intracellular Ca

Question 21

What is the mechanism of RyR?

Answer 21

involved in CICR –> cardiac skeletal muscle contraction

Question 22

Which drug/alkaloid activates/closes RyR? At what concentrations does it open/close?

Answer 22

drug: RYANODINE
open: nanomolar concentrations
close: micromolar concentrations

Question 23

Which receptor does CAFFEINE act on, and what is its effect?

Answer 23

• sensitizes RyR
• causes Ca2+ release from ER/SR

Question 24

Which drug blocks RyR?

Answer 24

DANTROLENE

Question 25

Which drug can be used to treat malignant hyperthermia?

Answer 25

DANTROLENE?

Question 26

Describe calmodulin.

Answer 26

- dimer - 4 EF Hand binding domains for Ca2+ - activates CaM kinase (calcium calmodulin kinase)

Question 27

TRUE or FALSE: the resting cell has very low Ca outside.

Answer 27

FALSE: low calcium inside the resting cell

Question 28

Which drug blocks Na/K ATPase?

Answer 28

DIGOXIN

Question 29

What does Na/K ATPase do?

Answer 29

3 Na out, 2 K in --> hyperpolarization

Question 30

Explain skeletal muscle contraction.

Answer 30

1. ACh activates nAChR 2. depolarization (ejp) 3. ejp reaches threshold --> AP --> open V-gated Na channels 4. AP along T-tubules --> activate L-type Ca channels 5. opening channel mechanically stimulates RyR1 on ER/SR --> Ca2+ release 6. Ca2+ removes troponin --> actin and myosin interact 7. contraction

Question 31

Explain cardiac muscle contraction.

Answer 31

1. depolarization --> activate L-type Ca channels 2. Ca activates RyR2 --> release Ca from ER/SR 3. Ca removes troponin --> actin and myosin interact 4. contraction (note: slight difference to skeletal muscle?) (i.e. CICR)

Question 32

Explain smooth muscle contraction.

Answer 32

agonists --> Gq --> PLC --> IP3 --> Ca2+ --> MLCK --> contraction

Question 33

Explain smooth muscle relaxation.

Answer 33

1. beta2 agonists --> cAMP --> phosphorylate MLCK --> deactivate MLCK 2. cGMP --> dephosphorylate MLCK --> vasorelaxation

Question 34

TRUE or FALSE: cAMP stimulate contraction and cGMP inhibits contraction.

Answer 34

FALSE: both cAMP and cGMP INHIBIT CONTRACTION