Mechanism of Heart Regulation Flashcards
Why is Heart Rate important?
is a predictor of how serious CVD can be; a resting HR>70bpm is considered to increase risk in individuals with CVD
Increased HR in atherosclerotic disease means
coronary artery plaque disruption is more likely to occur
rupture and thrombus formation induce arterial occlusion and MI
HR acts as a determinant for
Myocardial Oxygen Consumption- how much energy we need to use for the heart to pump properly
Higher HR requires greater blood flow and oxygen so the heart is less efficient
Heart rate is an important indicator, but why?
Can be used to predict CVD morbidity/mortality in acute and chronic disease
Resting HR >70bpm is considered a high risk
Why is high heart rate a risk factor?
Increased HR is linked to atherosclerosis/coronary artery plaque disruption
Determinant of myocardial oxgen consumption (amount of oxygen that the heart requires to maintain optimal function)
Determinants of coronary circulation perfusion time
A low HR leads to…
Decreased oxygen demands of heart
Increased coronary perfusion
A low HR is a target for treating:
Post-MI
Angina
Heart failure
(Beta1 blockers, calcium channel blockers)
What is the SAN?
Primary area generating pacemaker potentials in the heart
Provides initial electrical stimulus for myogenic activity of the heart (without nerve or hormonal input)
Direct relationship between pacemaker frequency and heart rate (HR)
Increased pacemaker frequency= increased HR
Where is the SAN located?
Initially thought to be located in the junction of superior vena cava and right atrium
‘Real’ SAN area is much more extensive
Measuring electrical activity: area affected by vagal stimuation (SAN is innervated by vagal stimuation)
Staining also shows SAN:
Neurofilament (SAN+atrial myocytes)
Cx43 (atrial myocytes)
ANP (atrial myocytes)
Area of no Cx43/ANP but neurofilament staining= SAN
Properties of SAN:
Electrical generating NOT contractile/conduction
Express HCN4 proteins- make up I f channels (I f= hyperpolarised sodium channels*)
HCN4 proteins are not present in other areas of the heart
Central SAN areas are surrounded by fibrosis.connective tissue
Do not express connexins e.g. Cx43
Poor gap junction structure
Pacemaker potentials leave SAN and spread into atria through specific pathways- currently unclear
SAN is not influenced by atrial electrical activity- could ‘switch off’ SAN
Relationship of pacemaker potentials, other cardiac action potentials and the ECG:
SAN generates pacemaker potential which spreads out into atrial muscle
Generates electrical activity in the atria muscle, electrical cativity spreads to the av node
Av node conduction through to bundle of his/ bundle branches down purkynje fibres to ventricular muscle
This produces the ECG
What distinguishes the action potentials from each other? (pacemaker potential–> diastolic depolarisation)
Stable vs unstable
Resting Membrane Potentials
Ionic basis of pacemaker potential
The SAN has an ability to generate its own electrical activity, whilst all other action potentials require a stimulus. This is due to the unstable resting membrane potential of the SAN:
An unstable resting membrane potential means that APs are generated all the time
The resting membrane potential is around -60mv which compares to the -90mv seen normally in cardiac cells
PHASE 4 is the unstable resting membrane potential
This leads onto PHASE 0 which is the activation of the up-stroke due to the activation of VGCC’s such that calcium influx causes an up-stroke in AP
VGCC’s start to switch off, whilst at the same time potassium channels start to be activated such that potassium leaves the cell down its concentration gradient, such that the cell becomes more negatively charged and is repolarised back to the resting membrane potential (PHASE 3)
At PHASE 4, If – hyperpolarisation-activated non-selective channels are activated; as the cell hyperpolarises and repolarises back to its resting membrane potential, If channels are switched on allowing for sodium influx – the cell becomes more positive and this depolarisation continues until it reaches the threshold to activate VGCCs. Therefore phase 4 is a relaxing phase of the heart
The process starts again and electrical activity is continually generated in SAN
But not so simple……. This voltage clock interacts with a ‘Ca clock’
What is the new understanding of pacemaker potentials?
PACEMAKER POTENTIALS ARE A COMPLEX INTERACTION BETWEEN VOLTAGE AND Ca2+ clocks
The calcium clock is thought to feed and initial the voltage clock
The sarcoplasmic reticulum calcium ATPase pump (SERCAII) uses ATP to take calcium against its concentration gradient into the SR (intracellular calcium storage)
Ryanadine receptors (RyR) are ligand-gated ion channels that are permeable to calcium; allow calcium to move from SR into cytoplasm
Therefore there is a ‘clock’ of reuptake and release
Cytosolic calcium is then thought to feed into the ‘voltage clock’ via the Na+/Ca2+ exchanger
What is the voltage clock?
Two phases:
LINEAR PHASE
I f channels: hyperpolarisation-activated cyclic nucelotide channels formed by HCN4 proteins; activated at <-45mV
EXPONENTIAL PHASE
VGCCs: L-type VDCC- activated –40mV, long lasting activation
T-type VDCC- activated –70mV, transient activation
INaCa: NaCa exchanger (NCX)- role linked to Ca2+ clock (calcium removed, sodium comes in)
