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PMCOL 343 > Cardiovascular 1 > Flashcards

Cardiovascular 1 Flashcards

1
Q

Where is Ca2+ stored in higher concentrations?

A

intracellular stores such as ER/SR and mitochondria

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2
Q

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

A

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

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3
Q

What are the 3 Ca entry mechanisms?

A

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

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4
Q

What is the mechanism of voltage gated Ca2+ channels?

A

open when cell is depolarized

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5
Q

What are the different types of voltage gated Ca channels?

A

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

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6
Q

Which drugs inhibit voltage gated Ca channels?

A
  • VERAPAMIL
  • DILTIAZEM
  • DIHYDROPYRIDINES (DHPs), e.g. NIFEDIPINE
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7
Q

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

A

DIHYDROPYRIDINES –> inhibit voltage-gated Ca channels

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8
Q

Which drug is used to treat angina and supraventricular arrhythmias?

A

VERAPAMIL and DILTIAZEM –> inhibit voltage-gated Ca channels

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9
Q

What is the mechanism of ligand-gated Ca channels?

A

opened by NTs or other agoinsts

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10
Q

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

A

NMDA glutamate channel

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11
Q

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

A

ATP-gated P2X channels

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12
Q

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

A

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
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13
Q

What are the 3 Ca extrusion mechanisms?

A

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

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14
Q

What is the mechanisms of PMCA?

A

pump cytoplasmic Ca2+ out of the cell

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15
Q

What is the mechanisms of SERCA pump?

A

pump cytoplasmic Ca2 into ER/SR

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16
Q

Which drug blocks SERCA pumps?

A

THAPSIGARGIN

17
Q

What is the mechanism of the NCX?

A
  • 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
18
Q

Explain reverse-mode NCX activity.

A

reduce Na gradient (inwards) –> intracellular Ca accumulation

19
Q

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

A

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

20
Q

What is the mechanisms of the IP3 receptor?

A
  • activated by IP3
  • Gq –> elevate intracellular Ca
21
Q

What is the mechanism of RyR?

A

involved in CICR –> cardiac skeletal muscle contraction

22
Q

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

A

drug: RYANODINE
open: nanomolar concentrations
close: micromolar concentrations

23
Q

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

A
  • sensitizes RyR
  • causes Ca2+ release from ER/SR
24
Q

Which drug blocks RyR?

A

DANTROLENE

25
Q

Which drug can be used to treat malignant hyperthermia?

A

DANTROLENE?

26
Q

Describe calmodulin.

A
  • dimer
  • 4 EF Hand binding domains for Ca2+
  • activates CaM kinase (calcium calmodulin kinase)
27
Q

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

A

FALSE: low calcium inside the resting cell

28
Q

Which drug blocks Na/K ATPase?

A

DIGOXIN

29
Q

What does Na/K ATPase do?

A

3 Na out, 2 K in –> hyperpolarization

30
Q

Explain skeletal muscle contraction.

A
  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
31
Q

Explain cardiac muscle contraction.

A
  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)
32
Q

Explain smooth muscle contraction.

A

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

33
Q

Explain smooth muscle relaxation.

A
  1. beta2 agonists –> cAMP –> phosphorylate MLCK –> deactivate MLCK
  2. cGMP –> dephosphorylate MLCK –> vasorelaxation
34
Q

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

A

FALSE: both cAMP and cGMP INHIBIT CONTRACTION

PMCOL 343 (27 decks)

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