11, 12. EC Coupling and Ca++ Handling Flashcards
What is this series of events?:
• Ca2+ enters via DHPR (“L-type Ca2+ channel”) and activates RyR2 to cause large flux of Ca2+ from SR into myoplasm.
• Ca2+ activates contraction by binding to troponin on thin filaments.
• Ca2+ is removed from the myoplasm by:
(i) SERCA2 pump located in longitudinal SR (2 Ca2+ per cycle); Ca2+ diffuses within SR to terminal cisternae, where it binds to calsequestrin (low affinity, high capacity)
(ii) NCX Na+/Ca2+ exchanger in junctional domains of plasma membrane and t-tubules.
excitation, contraction, and relaxation of Cardiac muscle
The sequence of events during excitation, contraction and relaxation of cardiac muscle cells is:
- • Ca2+ enters via _____ and activates RyR2 to cause large flux of Ca2+ from SR into myoplasm.
- • Ca2+ activates contraction by binding to ____ on thin filaments.
- • Ca2+ is removed from the myoplasm by:
(i) _____ located in longitudinal SR (2 Ca2+ per cycle); Ca2+ diffuses within SR to terminal cisternae, where it binds to calsequestrin (low affinity, high capacity)
(ii) NCX Na+/Ca2+ exchanger in junctional domains of plasma membrane and _____
- DHPR (“L-type Ca2+ channel”)
- troponin
i. SERCA2 pump
ii. t-tubules
The sequence of events during excitation, contraction and relaxation of cardiac muscle cells is:
- • Ca2+ enters via DHPR (“L-type Ca2+ channel”) and activates _____ to cause large flux of Ca2+ from SR into myoplasm.
- • Ca2+ activates contraction by binding to troponin on ______.
- • Ca2+ is removed from the myoplasm by:
(i) SERCA2 pump located in _____ (2 Ca2+ per cycle); Ca2+ diffuses within SR to terminal cisternae, where it binds to calsequestrin (low affinity, high capacity)
(ii) _____ in junctional domains of plasma membrane and t-tubules.
- RyR2
- thin filaments
i. longitudinal SR
ii. NCX Na+/Ca2+ exchanger
The sequence of events during excitation, contraction and relaxation of cardiac muscle cells is:
- • Ca2+ enters via DHPR (“L-type Ca2+ channel”) and activates RyR2 to cause large flux of Ca2+ from ____ into _____.
- • ___ activates contraction by binding to troponin on thin filaments.
- • Ca2+ is removed from the myoplasm by:
(i) SERCA2 pump located in longitudinal SR (2 Ca2+ per cycle); Ca2+ diffuses within SR to terminal cisternae, where it binds to _____ (low affinity, high capacity)
(ii) NCX Na+/Ca2+ exchanger in _____ of plasma membrane and t-tubules.
- SR into myoplasm
- Ca2+
i. calsequestrin
ii. junctional domains
What is a junctional domain?
junction btw the terminal cisternae of the SR and the plasma membrane
What is the junction btw the terminal cisternae of the SR and the plasma membrane called?
a junctional domain
What is a t-tubule?
plasma membrane invaginations
What plays the more important role: SERCA or NCX?
SERCA bc the SR surrounds each myofibril and this will req less energy
What is heart failure?
insufficient cardiac output, typically due to lack of contractile force
What is insufficient cardiac output, typically due to lack of contractile force called?
heart failure
How do cardiac glycosides work? Give an example of one.
inhibit Na/K ATPase and thus reduce extrusion of Ca++ via NCX; digitalis
Where is norepinephrine released from?
sympathetic nerve terminals
Epi and norepi act to:
- Increase Heart Rate (positive chronotropy) by _____
- Increase Contractile Force (positive inotropy)
- Increase Rate of Relaxation (positive lusitropy)
raising the firing rate of pacemaker cells in the SA node
Epi and norepi act to:
1. Increase Heart Rate (positive chronotropy) by raising
the firing rate of pacemaker cells in the SA node.
2. _____
3. Increase Rate of Relaxation (positive lusitropy)
Increase Contractile Force (positive inotropy)
Epi and norepi act to:
1. Increase Heart Rate (positive chronotropy) by raising
the firing rate of pacemaker cells in the SA node.
2. Increase Contractile Force (positive inotropy)
3. _____
Increase Rate of Relaxation (positive lusitropy)
Four important targets for PKA in cardiomyocytes are?
- The L-type Ca2+ channel
- RyR2
- Phospholamban (PLB)
- Troponin
_____ of the L-type Ca2+ channel increases the amplitude of the L-type Ca2+ current, increasing:
(i) the trigger for activation of _____
(ii) the ____ content
Phosphorylation
i. RyR2
ii. SR Ca2+
Phosphorylation of the _____ increases the amplitude of the L-type Ca2+ current, increasing:
(i) the trigger for activation of RyR2 and
(ii) the SR Ca2+ content
L-type Ca2+ channel
Phosphorylation of the L-type Ca2+ channel increases the _____, increasing:
(i) the trigger for activation of RyR2 and
(ii) the SR Ca2+ content
amplitude of the L-type Ca2+ current
Phosphorylation of ____ increases its activation by Ca2+.
RyR2
Phosphorylation of RyR2 increases its activation by ____.
Ca2+
____ inhibits SERCA2 Ca2+ pumping activity.
PLB
PLB inhibits _____ Ca2+ pumping activity.
SERCA2
PLB inhibits SERCA2 _____ pumping activity.
Ca++
What is Timothy Syndrome?
- genetic disorder causing arrhythmias, syncope, and sudden death
- causes immune deficiencies, cognitive abnormalities, autism
- de novo mutations of CaV1.2
- TS and TS2 variants have AV block, suppress voltage-dependent inactivation; prolonged Q-T intervals and PVT
- genetic disorder causing arrhythmias, syncope, and sudden death
- causes immune deficiencies, cognitive abnormalities, autism
- de novo mutations of CaV1.2
- TS and TS2 variants have AV block, suppress voltage-dependent inactivation; prolonged Q-T intervals and PVT
Timothy Syndrome
What is Brugada Syndrome?
- mutations of cardiac sodium channels NaV1.5, KChip2, and ankyrin
- significantly shortened Q-T interval
- large reduction in the magnitude of L-type Ca2+ current
What is another name for Brugada Syndrome?
Sudden Unexplained Death Syndrome
- mutations of cardiac sodium channels NaV1.5, KChip2, and ankyrin
- significantly shortened Q-T interval
- large reduction in the magnitude of L-type Ca2+ current
Brugada Syndrome
What is Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)?
- dominant mutations of RyR2 or recessive calsequestrin2 mutations
- no ECG abnormalities
- abnormalities upon exercise or infusion of catecholamines
- Activation of beta-adrenergic receptors causes arrhythmias
- dominant mutations of RyR2 or recessive calsequestrin2 mutations
- no ECG abnormalities
- abnormalities upon exercise or infusion of catecholamines
- Activation of beta-adrenergic receptors causes arrhythmias
Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)
How is CPVT treated?
beta-blockers
_____ blocks RyR2, but at doses too high to be clinically useful.
Tetracaine
Tetracaine blocks ____, but at doses too high to be clinically useful.
RyR2
_____ is a class 1C anti-arrhythmic that blocks cardiac sodium channels.
Flecainide
Flecainide is a class ____ anti-arrhythmic that blocks cardiac sodium channels.
1C
Flecainide is a class 1C anti-arrhythmic that blocks cardiac ____ channels.
sodium
What is calcium-dependent inactivation (CDI)?
inactivation of the L-type Ca++ channel on its cytoplasmic side, determined by Ca++ concentration
helps maintain a constant SR Ca++ content
What helps to maintain a constant SR Ca2+ content?
calcium-dependent inactivation (CDI)
