action potentials and contraction in cardiac and smooth muscle

Question 1

how is a RMP (restimg membrane potential) set up in cardiac myocytes?

Answer 1

cardiac myoctes are permeable to potassium ions at rest

K+ flow out of the cell down their concentration gradient created by Na+ K+ ATPase

they effflux out the cell until they reach an equal and opposite force not allowing them to leave (the electrical gradient no longer favours moving out as the outside is becoming more +) it has reached equilibrium E_k -95mV

small permability to other species at rest makes the RMP -90 to -85mV

Question 2

what is different about the length of heart action potentials length?

Answer 2

• both SAN and cardiacventricle myocytes have a longer AP

SAN also has a quirky shape

Question 3

talk me through ventricular cardiac AP

Answer 3

1. opening of volatge gated Na+ channels causes depolarisation
2. transient outward K+ flow and reversal of NCX brings AP down a bit
3. but then volatge gated Ca2+ open (which act to depolarise by flowing in). A few K+ channels are also open to counteract this creating a plateaux in AP
4. Ca2+ channels inactivate and lots of volatge gated K+ channels open and K+ efflux repolarising the cell

Question 4

talk me through the SA node action potential

Answer 4

SA node is a group of specialsed myocytes that generate electrical activity -60 is the lowest MP

1. pace maker potential is a slow depolarisation to threshold - it is from an influx of Na+ and is AKA funny current (I_f). It is considered funny as the channel behanves oddly - it opens in response to hyperpolarisation not the usual depolarisation
2. upstroke caused by voltage gated Ca2+ ion channels opening - not Na+ as these are inactivated at this potential
3. opening of voltage gated K+ channels and efflux of K+
4. there is no resting potential it just begins to slowly rise again

Question 5

why is the funny current funny?

what does this allow?

Answer 5

the HCN channels (Hyperpolarisation-activated Cyclic Nucelotide-gated channels) are activated by hyperpolarisation rather than depolarisation. The more negative the potential the more it activates (activates at more negative thn -50mV)- it alllows the influx of Na+ that depolarises the cell

this allows self automactity

Question 6

which is slower at depolarising? AV node or SA node?

Answer 6

AV node

Question 7

what takes over cinducting if AV node fails?

Answer 7

purkinje fibres - ensure AP gets to ventricles

this also has a slow depolarisation to threshold

Question 8

what happens if action potential fires slowly?

action potentals fail?

too fast?

random?

Answer 8

• bradycardia (less than 60bpm)
• asystole
• tachycardia (more than 100bmp)
• fibrilation (AF or VF)

Question 9

effects of hyperkalaemia on heart?

what is the treatment?

what value in plasma is too high?

Answer 9

• raise extracellular K+ increases E_k (less negative) so the membrane is slightly depolarised

may initalliy increase ecxtability and HR

however moderate to severe hyperkalaemia would depolarise enough to inactivate the V-gated Na+ channels. this leads to slow upstroke and shorter AP (more rapid repolarisation)

heart can stop:(

• insulin and glucose (insulin increses K+ uptake into cells), Calcium gluconate (divalent calcium reduces excitability)
• more than 5.5mmol/L

Question 10

what is the effect of hypokalaemia?

what is considered hypokalaemic?

Answer 10

• lengthens AP - delays repolarisation. longer AP create opportunity dor early after depolarisations (EAD). This can lead to oscillations of membrane potential due to Ca2+ channel recovery and opening. Can cause VF. This is because K+ channels reduce conducatnce/activity in lower K+ levels so repolarisation is slower
• less than 3.5mmol/L

Question 11

talk me through cardiac myocyte contraction.

Answer 11

1. AP travels down transverse tubule
2. L type Ca2+ channels move Ca2+ into myocyte (25% of calcium entereing enters this way)
3. This causes calcium induced calcium release CICR from ryanodine receptors in SR (75% of Ca entering enters this way)
4. Ca2+ binds to troponin C causing conformational change
5. conformational change reveals moves tropomyosina nd releals binding sites
6. sliding filament theory

Question 12

what happens in relaxation of cardiac myocytes?

Answer 12

Ca2+ needs to return to resting levels as it is toxic to the cell:

most is pumped into the SR by the SERCA (high capacity, low affinity)- sarcoplasmic reticulum calcoum ATPase

some exits across the sarcolemma via NCX and Plasma Memebrane Ca2+ ATPase (PMCA)

Question 13

talk me through contraction on vascular smooth muscle (blood vessel walls).

Answer 13

1. depolarisation opens voltage gated calcium channel VGCC
2. calcium flows in
3. 4 Ca2+ ions bind to 1 camodulin molecule (CaM)
4. CaM activates MLCK (myosin light chiain kinase)
5. MLCK phosphorylates myosin light chain on mysoin head
6. myosin head can now bind to actin and contract
7. MLCP (myosin light chain phosphatatse) dephosphorylates myosin light chain to terminate contratcion = relax

Question 14

what is the alpha 1 adrenoreceptors role in vascular smooth muscle contraction?

Answer 14

A1 Gq GPCR when activated, phospholipase C cleaves PIP and produces IP3 and DAG

IP3 acts on SR and causes Ca2+ release for contraction

DAG activates PKC which inhibits MLCP to mainatin contraction

Question 15

what inhibits MLCK

Answer 15

PKA phosphoylates it and can inactivate it - this means MLCK cannot phosphorylate myosin light chain and contract