2.02 - Modulation Of The Cardiac Action Potential Flashcards
Describe the EC coupling in cardiac myocytes
Flow of calcium in to cell from extracellular environment via L-type calcium channels also with release of calcium from sarcoplasmic reticulum stores
Calcium causes shortening of contractile proteins
Pumps clear calcium from sarcoplasma (Na/Ca pump) and it is also taken up into SR and stored in calsequestrin.
Describe the effect of sympathetic stimulation on the contractility of the heart.
Sympathetic stimulation of the beta1 receptors (isoproterenol) in the heart results in a greater calcium influx –> bigger force of contraciton with faster rate of shortening
Other targets of second messengers include: L-type calcium channels, contractile proteins, cytosolic calcium concentration and store refilling via SERCA/Phospholambin
What are the five types of cardiac tropisms
Chronotropisms
Bathmotropisms
Dromotropisms
Inotropism
Lusitropism
Describe chronotropism
Relates to heart rate
a reduction in the time between heart beats (increased heart rate) is positive chronotropism
Describe bathmotropism
Relates to the threshold of the action potential
Describe dromotropism
Relates to the conduction delay in the atrioventricular node
Shortened delay in the AV node is positive dromotropism
Describe Inotropism
Relates to contractile force of the heart
Increased force is positive inotropism
Describe Lusitropism
Relates to rate of relaxation of the cardiac muscle
A faster relaxation rate is positively lusitropic
Describe the sympathetic innervation of the heart
T1-T5
Noradrenaline is the neurotransmitter
Effect: excitatory (increased heart rate, stroke volume, peripheral resistance)
Slow
Diffuse innervation (whole heart) as we need to get the sympathetic activation to the cardiac myocytes
Describe the parasympathetic innervation of the heart
Cranial Nerve X = Vagal
Acetylcholine (muscarinic receptors, M2)
Inhibitory action (decreased heart rate and SV)
Fast
Restricted innervation - nodes only (SA & AV)
Describe the autonomic control of heart rate
Both sympathetic and parasympathetic are tonically active. para is larger and predominates over sympa output
Blockage of both systems leads to a heart rate of ~100bpm
Describe the effect of sympathetic stimulation of the SAN
Stimulation of the SAN by the sympathetic nervous system results in, over several beats, increased heart rate and AV conduction, AP shortening, increased AP amplitude, and increased rate of pacemaker delay (positive-tropisms).
Describe the molecular signalling in sympathetic stimulation of the heart
Activation of beta one receptor (GPCR) –> activation of Ga –> stimulation of adenylyl cyclase –> conversion of ATP to cAMP.
cAMP has a direct effect on the If (funny; HCN) channel. It increases the probability of it being open –> increased influx of Na –> faster decay of RMP –> increased heart rate
cAMP increases the production of Protein Kinase A (PKA). PKA has effects on the delayed rectifier –> increasing K efflux –> faster repolarisation –> increased hate rate.
PKA also increases intracellular calcium and promotes its clearance –> increased force of contraction and faster clearance
Describe the parasympathetic stimulation of the SAN
Parasympathetic innervation only to ICS (nodes) not to myocyes as well
M2 receptors.
Fast effect. Leads to instantaneous drop in heart rate.
Nerve stimulation leads to PMP decay decrease with a decreased AP amplitude
Describe the molecular signalling in parasympathetic stimulation of the heart
Acetylcholine activates M2 (GPCR) receptors in the ICS. Galpha inhibits adenylyl cyclase leading to decreased conversion of ATP to cAMP.
Reverse effects as sympathetic stimulation
less cAMP so decreased activity of funny channel –> slower RMP decay.
Decreased PKA production –> less K channel activity –> slower repolarisation, longer action potential –> decreased heart rate
Summarise the effect of parasympathetic and sympathetic stimulation on:
cAMP, the pacemaker potential, calcium influx, interval between APs and where in the heart they act.
