Calcium and the Heart Flashcards
(14 cards)
Myocardial fibres
contractile cells
- 99% of all cardiac muscle cells
- responsible for mechanical pumping
- don’t normally initiate own AP
conductive fibres
- autorhythmic cells
- do not contract
- initiate and conduct APs
- Purkinje fibres and SAN
Cardiac output
CO = HR x SV
- HR affected by SNS and PNS
- SNS also alters contraction strength, which affects SV
- stretch also affects SV via altering contraction strength
- end diastolic volume affects SV, and also, via Starling’s law, causes stretch
Cardiac output - contraction strength
ways to alter contraction strength
1. change sensitivity of myofilaments to calcium
2. change amplitude and duration of calcium transient
Cardiac output - receptor-mediated pathways
beta-adrenergic stimulation results in:
- ionotropy (increased contraction)
- leucotropy (increased rate of relaxation)
beta acts via Rad
- interacts with beta subunit of L-type Cavs
- phosphorylation by PKA
- Rad required for L-type regulation
Cardiac output - Gq-mediated regulation
hormones that trigger IP3 production in the heart lead to ionotropy and arrhythmias
Starling law
increased preload = increased myocardial stretch
- neurohormone-independent
- via troponin C sensitisation to calcium? = increased rate of cross-bridge assembly and disassembly
Slow force response
- subsequent to Starling
- induced by stretch but not required
- ATII and ETI dependent in atria and NHE/NCX in ventricles
- increased phosphorylation of MIC2
- MICK inhibition prevents this and results in increased calcium sensitivity
Atria
- contribute little to cardiac contractility and function
- atria devoid of t-tubules
- some t-tubules in larger mammals, but still less than ventricles
- ring of calcium around atrial cardiomyocyte
SAN AP
- slow depolarisation by Funny currents
- at threshold, L-type calcium channels open
- repolarisation by potassium channels
Ventricular AP
- sodium entry for depolarisation
- calcium entry maintains length of the AP
- potassium current repolarises
Excitation-contraction coupling
- coupling of electrical depolarisation of the sarcolemma with contraction
- SERCA2a isoform present in cardiomyocytes
- phospholamban = SERCA inhibitor
T-tubules
t-tubules = invaginations of the sarcolemma that stretch the whole length of the cell
- at the z-line of the sarcolemma
- to allow the whole cytosol to experience depolarisation
Ryanodine receptors
- calcium-induced calcium release
- homotetramers
- 4 subunits form a square around the pore
- major calcium release channel
Excitation-contraction coupling - calcium
- L-type Cavs are located very close to RyRs (DYAD)
- each cluster creates a calcium spark
- sparks summate to form a calcium transient
- summation of elementary calcium sparks gives rise to a global calcium signal
non-coupled RyRs makes coupling inefficient as calcium diffusion required to reach RyRs
