EC Coupling I and II Flashcards Preview

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Flashcards in EC Coupling I and II Deck (24):
1

Which phase is the L-type Ca channel responsible for

Phase 2 - plateau

2

What ion if removed from extracellular space would cause EC coupling to fail?

Calcium!

3

Cardiac muscle EC coupling vs Skeletal

Cardiac: ECC requires entry of external Ca2+
Skeletal: Does NOT require entry of external Ca2+
DHPR: Cav1.2 for cardiac, Cav1.1 for Skeletal
BOTH: Ca2+ binds to troponin on thin filaments and activates contraction

4

Explain Patch Clamp Test

Cells on a dish that you can stick an electrode in and measure the movement of Ca by Ca fluorescence

Can also measure with glass electrode?

5

calsequestrin has high _____ but low _____ which keeps Ca from sticking so concentration of Ca doesn't go so high

high capacity, low affinity

- SERCA2 pump moves calcium into the terminal cisternae (JSR) to be bound by calsequestrin

6

NCX gives ___ Na in for ___ Ca out

3 Na : 1 Ca

(so +1 charge total influx)

7

Where does energy for NCX come from?

Na running down its electrochemical gradient; also a net charge transfer of 1 so a voltage gradient also helps push Ca out of cell

8

SERCA2 dominates over NCX because _____ SR surrounds each myofibril and requires ____ energy because Vsr = 0

longitudinal SR, requires less energy

*note: NCX is next in importance and can be arrhythmogenic

9

In steady-state, Ca2+ released from SR is recycled back into SR by ______, and surface extrusion balances _______

SERCA2, balances L-type Ca2+ current

10

If DHPs equally blocked L-type channels in cardiac and vascular muscle, the reduced vascular resistance would be offset by a reduced force of cardiac contraction. Why doesn’t this occur?

1. Slice isoform are more sensitive to dihydropyridines
2. Effect is complicated and depends upon voltage so that SM has more depolarized RP. More effective

11

NE released by nerve terminals and circulating epinephrine act to:

1. Increase HR by raising firing rate of pacemaker cells in the SA node
2. Alter propagation through the conduction pathways
3. Increase Contractile Force (positive inotropy)
4. Increase Rate of Relaxation (positive lusitropy)

12

Four important targets for PKA in cardiomyocytes

1. L-Type Ca2+ channel
2. RyR2
3. Phospholamban
4. Troponin

13

Phosphorylation of L-type Ca2+ channel ____ the amplitude of current

Increase. The bigger the trigger, the bigger the Ca2+ release, which means larger activation and contraction

14

Phosphorylation of RyR2 causes what?

Increases its activation by Ca2+, making it more likely to open

15

Phosphorylation of PLB does what?

Causes dissociation from SERCA2 which increases Ca2+ pumping into SR. Speeds relaxation and increases SR Ca2+ content

16

Phosphorylation of troponin does what?

Leads to positive lusitropy because rate of Ca2+ coming off of troponin is speeded up.

17

Timothy Syndrome

Linked to de novo mutations in:

de novo Cav1.2 - leads to cardiac arrhythmias, immune deficiency, and cognitive abnormalities

TS2 mutations suppress voltage-dependent inactivation of Ca current, results in Long QT syndrome (AV block)

18

Brugada Sydrome (Sudden Unexplained Death Syndrome)

Linked to mutations of Nav1.5, KCHip2 and other proteins (ankyrin)

Appear to cause a large reduction in the magnitude of L-type Ca2+ current = impaired membrane trafficking

Significantly shortened QT interval, shortened ventricular AP

19

Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)
- what kind of ECG does it display?
- Most mutations result from (select one) dominant/recessive mutations in _____
- What does the mutation cause?
- Similar mutations cause what diseases?
- What can CVPT trigger?

Do not display ECG abnormalities at rest, but do upon exercise or infusion of catecholamines

Result from dominant mutations in RyR2 = increase resting "leak" of Ca2+ out of the SR

Can also make RyR2 more sensitive to activation by Ca2+

Similar RyR1 mutations cause malignant hyperthermia and central core disease

See occurrence shortly or long after repolarization - can trigger ectopic APs

20

Recessive inheritance of CPVT is through what molecule?

Calsequestrin 2

Regulates the function of RyR2 and this may be altered by CPVT mutations

21

What is standard therapy for CPVT? Why?

Beta-blockers because of the activation of B-adrenergic receptors being proarrhythmogenic.
- They are pro-arrhythmogenic because they increase SR Ca content and phosphorylation of RyR2

Flecainide bc it is a class 1C anti-arrhythmic that blocks cardiac sodium channels →block the open channels → reducing the frequency of spontaneous Ca release in ventricular myocytes

22

voltage-gated L-type Ca2+ channels are also known as?

dihydropyridine receptor or DHPR (dihydro-pyridine rcptr)

23

During depolarization, the NCX exchange becomes a significant course of Ca2+ extrusion how?

NCX driven depolarization

During depolarization, 3 Na+ ions enters and 1 Ca2+ ion exit the cell.
- causes net inward current into the cell
- this can cause membrane depolarization and trigger APs

24

Depolarization triggered by Ca2+ release from the SR has the capacity to trigger what dangerous effect?

Arrythmias