Cellular and Molecular mechanisms the Heart and Vasculature Flashcards
hoe does K+ permeability set the RMP in cardiac myocytes
- cardiac myocytes are permeable to K+ ions at rest.
- K+ ions move out of the cell down the conc gradient which makes the inside negative with respect to the outside. As charge builds up an electrical gradient is established.
how excitation leads to contraction in cardiac myocytes.
-cardiac myocytes are electrically active so can fire action potentials which cause a big depolarisation.
-As cardiac myocytes are electrically coupled to each other when 1 depolarises it spreads to the others also depolarising them and contract together in a coordinated way.
the action potential triggers increase in cytosolic [Ca2+] which is required to allow actin and myosin interaction
explain the different phases of the ventricular action potential
1) opening of V-gated Na+ channels
2) transient outward k+ current
3) opening of v gated Ca2+ channels
4) Ca2+ channels inactivate. v-gated k+ channels open
explain the SA node action potential
1) pacemaker potential I(f)- influx of Na +
2) opening of v gated Ca2+ channels
3) opening of v-gated k+ channels
why is the SA node the pacemaker
- fastest to depolarise
- sets rhythm
- AP initiated here.
what happens if action potentials fire too slowly in the heart
bradycardia
what happens if action potentials fail in the heart
asystole-no contraction
what happens if action potentials fire too quickly in the heart
tachycardia
what happens if electrical activity in the heart is random
fibrillation
why are cardiac myocytes so sensitive to changes in K+
K+ permeability dominates the resting membrane potential
heart has many different kinds of k+ channels
effect of hyperkalemia in heart
Ek gets less negative so membrane potential depolarises a bit
this inactivates some voltage gated Na+ channels slowing down upstroke.
risks with hyperkalaemia in heart
heart can stop
may initially get an increase in excitability
treatment of hyperkalaemia
calcium glutinate
insulin+gluose - insulin will drive k+ into cells but you don’t want glucose levels to go down so you also give glucose.
effects of hypokalaemia
k+ channels reduce their conductance prolonging duration of action potential
delays depolarisation
what is the problem with hypokalaemia
longer action potentials can lead to early after depolarisations (EADs) which can lead to oscillations in membrane potential.
can result in ventricular fibrillation
how does relaxation of cardiac myocytes occur
must return [Ca2+]I to resting levels
most is pumped back into SR (SERCA)- raised Ca2+ levels stimulates these pumps
some also exits across cell membrane
how does excitation contraction coupling occur in smooth muscle
depolarisation can open V gated Ca2+ channels and Ca2+ can bind to CaM as there is no troponin in smooth muscle. the ca2+ CaM complex activates MLCK which phosphorylates regulatory light chain. myosin light chain must be phosphorylated to enable actin-myosin interaction.
another way : noradrenaline activates a1 receptors forming Gaq (G alpha q). sends IP3 as second messenger. SR has IP3 receptors that release Ca2+ which then follows the same pathway as before
how is contraction of vasculature inhibited
- myosin light chain phosphatase dephosphorylates the myosin light chain
- MLCK itself can be phosphorylated by PKA inhibiting MLCK therefore inhibiting phosphorylation of myosin light chain and inhibits contraction
differences between cardiac muscle and smooth muscle
- contraction of the heart is initiated by spread of APs from SA node.
- cardiac myocyte action potentials allows Ca2+. further Ca2+ is released from SR , increased intracellular Ca2+, Ca2+ binding to troponin C.
- contraction of vascular smooth muscle cells initiated by depolarisation or activation of a adrenoceptors. increased intracellular Ca2+, Ca2+ binding to calmodulin activating MLCK-phosphorylates myosin light chain
