Physiology and Pharmacology 19: initiation of the heartbeat Flashcards
Where is heart muscle contraction initiated? What is electrical activity in the heart known as?
Sino-atrial node (SAN)
Electrical activity is myogenic
How are cardiac muscle cells connected? Characteristics?
Via intercalated discs
- contain many gap junctions -> allows electrical conduction
Describe spread of electrical conduction in the heart
Initiated at SAN (pacemaker)
- > atrium
- > atrio-ventricular node (delay)
- > ventricle via bundle of his
Why is there a delay at the AVN?
Allows atria to finish contracting
->
What gives rise to the pacemaking properties of the sino-atrial node?
Cells in SAN do not have stable resting potential
Rising phase of action potential depends of Ca2+ influx through voltage-gated calcium channels (L-type) activated by depolarisation
Falling phase dependent on K+ exit through voltage activated potassium channels
What mechanisms give rise to the small rise in membrane potential during the ‘pacemaker potential’ (small depolarisation at end of AP in SAN)
1) Slow closing of potassium channels -> channels eventually close and prevent K+ from leaving cell
2) NCX sodium-calcium exchanger exchanges 3 sodium into the cell, 2 calcium out of cell (net positive increase)
3) If (funny current) contributes to depolarisation
4) ICaT channels activate at slightly lower potentials than regular Ca2+ channels contribute to depolarisation
5) SA cells have very little inward rectifier K+ current (meaning higher baseline membrane potential)
With this combination -> Inward current predominate -> slow depolarisation tends towards threshold and triggers AP -> ‘pacemaking’ of heartbeat
Describe the shape of a ventricular AP and explain the mechanisms behind this pattern
More negative initial membrane potential (due to large inward rectifier K+ current at rest)
Extremely sharp incline + fast depolarisation due to opening of voltage gated sodium channels
Followed by long plateau -> results from balance of inward Ca2+ and outward K+ currents
-> then decline as K+ outward current predominates
duration of 100-300ms ensures enough Ca2+ enters to initiate contraction -> one AP spreading through heart = one heartbeat
Why does SAN use Ca2+ in depolarisation during AP?
Sodium channels would be inactivated due to the higher, less negative membrane potentials before AP
Compare electrical properties of SA node cells and ventricular cells - comment on:
Resting potential AP upstroke AP repolarisation Presence of voltage-gated Na+ channels Presence of inward-rectifier K+ channels
Resting potential
SA: unstable, slow depolarisation after each AP
V: stable at about -85mV between APs
AP upstroke
SA: L-type Ca2+ channels
V: Voltage gated NA+ channels
AP repolarisation
SA: Voltage gated K+ channels
V: Voltage gated K+ channels AND inward rectifier K+ channels
Voltage gated Na+ channels?
SA: absent V: Present
Inward rectifier K+?
SA: absent (for most part) V: Present
Mechanism of muscle contraction upon Ca2+ influx?
Ca2+ binds to troponin C
-> acts through troponin-tropomyosin complex associated with the actin filament to allow myosin heads to attach + form cross-bridges
-> followed by cross-bridge cycling and contraction
Describe mechanism for rise of intracellular Ca2+ in cardiac cells
Action potential travels over cell surface membrane and down T-tubules
Depolarisation activates L-type Ca2+ channels
-> Ca2+ entry
Rise in intracellular Ca2+ activates ryanodine receptors (RyR) -> further Ca2+ released from SR
- this part known as calcium induced calcium release (CICR)
Ca2+ entry ~20%, CICR ~80%
Will removing calcium from outside of the cell stop contraction completely?
Yes -> because extracellular calcium is required to trigger CICR
Mechanisms underlying fall of Ca2+ -> relaxtion in diastole?
L-type Ca2+ channel close due to inactivation
The SERCA transports Ca2+ back into SR
Ca2+ is transported out across the plasma membrane primarily by the Na/Ca exchanger (NCX)
Why do athletes have a much lower heartrate at rest?
Significantly larger stroke volume -> less heart rate required to meet resting CO demands
remember CO = SV * HR
