Contraction and Relaxation Flashcards
what channels allow the entry of Ca into the cardio myocyte
RyR2
where does intracellular Ca get released from?
Sarcoplasmic reticulum
where does the Ca bind to
troponin C on actin filaments in the sarcomere
how does the heart muscle relax?
K channels open
what receptor takes the Ca back into the sarcoplasmic reticulum
SERCA2a
what receptor removes Ca from the cell
NXC (Na+/Ca2+ exchanger)
how many ryanodine receptor isotypes are there?
3
which isotype is found in the heart
RyR2
how are RyR2 receptors arranged?
clusters
what does activation of the RyR2 clusters cause
calcium spark
what can lead to leaky RyRs
caffeine
where/what are RyRs
Ryanodine receptors (RyRs) are located in the sarcoplasmic/endoplasmic reticulum membrane and are responsible for the release of Ca2+ from intracellular stores during excitation-contraction coupling in both cardiac and skeletal muscle
consequence of a leaky RyR
calcium escape from the intracellular stores into the cytosol possibly causing a premature atrial contraction
effect of low [caffeine]
increased sensitivity to RyRs to cytosolic Ca2+
What is SERCA2a
SERCA is a type P ATPase pump that transports two calcium ions in exchange of the hydrolysis of one ATP molecule, functioning against a calcium gradient to restore luminal ER calcium levels
what activates SERCA2a
increased cytosolic Ca
what regulates SERCA2a
PLN
How can PLN activate SERCA2a
if high [Ca] AND PLN is phosphorylated itself (on CAMK11 and PKA sites)
what is NCX
Na/Ca exchanger
what drives the NCX
increased cytosolic [Na] or [Ca]
how can this operate
forward or reverse
which is the normal direction?
forward (Ca x 1 out, Na x 3 in)
what activates the forward direction of the NCX
increased cytosolic Ca
what is an adverse side effect of NCX
can cause membrane depolarisation, which triggers DADs in Ca2+ overloaded myocytes
how does the forward reaction affect the cytosolic [Ca]
decreases it
how is Ca2+ homeostasis regulated in the cardiac myocyte
sympathetic nervous system
4 main phosphorylation sites
Cav1.2 (calcium channel)
RyR2 (on SP)
Troponin 1
PLN-mediated SERCA
PLN-mediated SERCA can also cause an
increase in force contraction
EADs can be caused by
hyperphosphorylation and enhanced activity of Cav1.2
what predominant effect do catecholamines have
positive inotropic
how do catecholamines have a positive inotropic effect
increase [Ca] in the cytosol via PKA mediated phosphorylation of L-VACC and Ca release via RyR2
how do catecholamines have a negative inotropic effect
increase Ca reuptake into the SR via PKA-mediated phosphorylation of SERCA (the PLB becomes phosphorylated)
4 examples of catecholamines that have a positive inotropic effect
NA, A, dobutamine, isoprenaline
what effect does digoxin have
inhibit Na/K ATPase
effect of digoxin
- binds to extracellular K+ site competitively, inactivating it,
- increasing [Na] in the cytoplasm
- REVERSE mode on NCX
- more Ca into the cell
- +ve inotropy
over dose of digoxin
- increased Ca in cytoplasm
- stimulate FORWARD NCX
- NCX is electrogenic, so more +ve charges enter than exit
- membrane depolarisation
- DADs –> arrhythmias
levosimendan
is a +ve inotrope
