Electrical and molecular mechanisms in the heart & vasculature Flashcards
how is the resting membrane of the heart set up?
Cardiac myocytes permeable to K+ at rest -> K+ move out of cell, down concentration gradient -> makes inside -ve with respect to outside -> electrical gradient established.
what is the resting membrane potential of cardiac myocytes?
-80 to -90 mV
why doesn’t the resting membrane potential = Ek?
there is a very small permeability to other ion species at rest. However permeability to K+ is the main determinant of RMP
what is the depolarisation of cardiac myocytes due to?
opening of voltage-gated Na+ channels -> influx of Na+
what are the 3 stages of repolarisation of cardiac myocytes?
- transient outward K+ current
- plateau due to opening of voltage-gated Ca2+ channels -> influx of Ca2+
- depolarisation due to efflux of K+ through voltage-gated K+ channels
give a brief summary of SA node action potential.
Natural automacity
unstable membrane potential - pacemaker potential (slow depolarisation to threshold), ‘funny current’, influx of Na+.
upstroke - opening of voltage-gated Ca2+ channels.
Downstroke (repolarisation) - opening of voltage-gated K+ channels
what are the consequences of excitation going wrong?
Action potentials fire too slowly -> Bradycardia
Action potentials fail -> asystole
Action potentials fire too quickly -> tachycardia
Electrical activity becomes random -> fibrillation
what is the normal range for [K+] in the blood?
must be kept between 3.5 and 5.5 mmol/L
what is the effect of hyperkalaemia on electrical activity of the heart?
depolarises the myocytes and slows down the upstroke of action potential
what are the risks of hyperkalaemia?
- heart can stop
- may initially get an increase in excitability
mild - 5.5-5.9 mmol
moderate - 6.0-6.4 mmol
severe - 6.5 mmol
what is the treatment for hyperkalaemia?
- calcium gluconate
- insulin + glucose
(these won’t work if the heart has already stopped)
what are the effects of hypokalaemia on electrical activity?
lengthens the action potential. Delays repolarisation
what problems can result from hypokalaemia?
longer action potentials can lead to early after depolarisations
this can lead to oscillations in membrane potential
can result in ventricular fibrillation
describe excitation-contraction coupling?
depolarisation opens L-type Ca2+ channels in T-tubule system
localised Ca2+ link between L-type channels and Ca2+ release channels
25% enters across sarcolemma, 75% released from sarcoplasmic reticulum
describe the regulation of contraction in vascular smooth muscle
Ca2+ binds to calmodulin -> activates MLCK
MLCK phosphorylates the myosin light chain to permit interaction with actin.
Relaxation as Ca2+ levels decline - MLCP dephosphorylates the myosin light chain
Phosphorylation of MLCK by PKA inhibits the action of MLCK
