Mechanisms Of Heart Rate Regulation Flashcards
Why are we interested in modulating heart rate (HR)? (2)
HR is a predictor of CVD morbidity/mortality in acute and chronic disease
Resting HR above 70 beat/min considered to increased risk
Why is increased resting heart rate considered a risk? (6)
-increased HR linked to atherosclerosis/coronary artery plaque disruption
-Determinant of myocardial O2 consumption
-Determinants of coronary circulation perfusion time
=
-decreased HR leads to a increased O2 demands of heart
-increased Coronary perfusion
-decreased HR is a target for treating post-MI, angina, heart failure etc.
Use of B1 blockers, Ca2+ channel blockers
Where is HR initiated and regulated?
Sino-atrial node (SAN)
What is the SAN? (3)
-Primary area generating pacemaker potentials in the heart
-Provides the initial electrical stimulus for myogenic activity of the heart
-Direct relationship b/w pacemaker frequency and heart rate (HR)
Where is the SAN?
Textbook answer: A small nodule of specialised cells at the junction of the SVC with
the RA
Is this correct?
The ‘real’ SAN
image (dorsal view)
Red: SAN node
Blue: peripheral SAN node
Area of SAN is a much more extensive structure than thought:
Measuring electrical activity : area affected by vagal stimulation
Staining : neurofilament (SAN + atrial myocytes), Cx43 (atrial myocytes),
ANP (atrial myocytes)
– area of no Cx43/ANP but neurofilament staining = SAN
Properties of SAN (6)
-SAN cells: electrical generating not contractile/conduction
-Express HCN4 proteins – make up If 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, like atrial myocytes),
-Poor gap junction structure
-SAN is electrically isolated from rest of heart
Why is SAN electrically isolated from rest of heart (2)
-Pacemaker potentials leave SAN and spread into atria through specific pathways – currently unclear
-SAN is not influenced by atrial electrical activity
= This could ‘switch-off’ SAN
Relationship of pacemaker potentials, other cardiac
action potentials - pathway (6)
image
1) SAN = contraction (diastolic depolarisation)
2) spread to Atrial muscle (both left +right) = electrical activity, coupled to = contraction
3) electrical activity spread to AVN = slows down A.P. = ejection + filling of ventricles = conduction to Bundle branches
4) Bundle of HIs, Bundle Branches
5) Purkinje Fibres
6) Ventricular tissues
ECG and Electrical activity
Electrical PATHWAY CREATES ECG (measuring this electrical pathway) = changes e.g. rate/rhythm conduction pathway
What distinguishes these action potentials from each other? Hence, causing the pacemaker potential? (3)
stable vs unstable resting membrane potentials
The pacemaker potential causes a diastolic depolarisation during the resting period of the heart
SAN begins to depolarise = creating another A.P = initiate another heartbeat
Ionic basis of pacemaker potential – Recap
image
Activation of If initiates diastolic depolarisation= forms ionic basis for initiating pacemaker activity, in absence of external stimuli
But not so simple…….
This voltage clock interacts with a ‘Ca clock’
New Understanding
image
Pacemaker potentials are a complex interaction b/w Voltage and Ca2+ clocks
What is the Voltage Clock? (5)
image
If channels: Hyperpolarisation-activated cyclic nucleotide (HCN) channels formed by HCN4 proteins; activated at <-45 mV
Linear phase
VGCCs: 1)L-type VDCC – activated -40 mV, long lasting activation;
2) T-type VDCC – activated -70 mV, transient activation
INaCa: NaCa exchanger (NCX) – what is this role? Linked to Ca2+ Clock
Exponential phase
What is the Ca2+ Clock? (3)
image
By removing the rise of [Ca2+]i = activate NCX = influx of Na+ = depolarisation
