electical activity long Flashcards
What are the Ionic concentrations in and outside of resting myocytes
Nernst potential for K+
[K+]i = [K+] inside cell 150mv
[K+]o = [K+] outisde cell 4mv
Formular for the membrane potential
If the equilibrium potential for each ion remains unchanged (ie the concentration gradient doesn’t change) the membrane potential depends on permability and conductance of the ions. So if only 1 ion is conducting (eg K+) the membrane potential will be that ion’s equilibrium potential
simplified membrane potential
the resting membrane potential is near the equilibrium potential for K+ as it has high conductance compared to the other ions.
The permeability/conductance of the cell membrane to ions is due to negatively cahrged protein in the cell
how are concentration gradients maintained
Energey dependant ionic pumps
- ATP dependent Ca++ pump (if Ca++ accumulates inside get cellular dysfunction
- Na+/Ca+ exchanger (3:1) in either direction
- Na+/K+ ATPase pump 3:2 (3 Na+ out for every 2 K+ in)
ATP (therfore O2) dependant, in the sarolemma in the membrane
Note: ability to maintain ionic concentration gradients means that Em chagnes are due to changes in ionic conductance
The 2 types of ion channels
- voltage gated - open and close in response to changes in membrane potential. Na, K, Ca voltage gated channels exist and are involved int he action potential
- Receptor gated channels. Eg acetylcholine released by the vagus nerve innervating the heart binds to a sarcolemmal receptors that causes special type of K channel to open
Fast Na channels - how they work normally and what happens if cell is hypoxic
- at resting membrane potential it is closed
- m gate opens with depolarization
- h gate closes after a few milliseconds stopping Na so get repolarization
- at end negative membrane potential causes m to close and then h to open
This channel responds differently if the resting membrane potential is partially depolarized or the cell slowly depolarizes. EG hypoxic cell means cell is partially deploarized which inactivates the Na cheannel by closing H gates
3 factors that determine the amount of ion that passes through membrane
- number of channels
- duration they are open
- The electrochemical gradient drving them
types of cardiac action potentials
non pacemaker cells - triggered by depolarzing currents from adjacent cells. Em -90mV
pacemaker cells - cabable of spontaneous ap generation. Em - 60mV
o Diff concentrations of Na, K and Ca in and outside cell ? correct
• K 135 in 5 out, Nernst -94
• Na+ 10 in 140 out, Nernst 70
• Ca++ <0.1 in, 2 out, Nernst 134
NOTE: both are different from ap’s of neural and skeletal muscle cells
what are the differences in action potentials between cells types
duration (due to different ionic conductance)
nerve 1 milisecond
skeletal muscle 2-5milisecond
ventricular 200-400milisecond
PO 1.43
ionic basis of normal cardiac excitation
non pacemaker action potential (atrial and ventricular myoctyes, purkinje cells)
250ms
phase 4 - resting membrane potential (near Ek), -90mV, due to inward rectifier K channel (Ik1), due to [K] as this is most permeable. regained by Na+/K+ ATPase and Na+/Ca+
phase 0 - cell rapidly depolarizes from -90mV to threshold voltage of -70mV due to ap conducted by adjacent cell because of fast Na+ channel conductance. gK falls because potassium inward rectifier channel becomes non conducting at positive potentials
phase 1 - initial repolarization when transient outward K+ (lto) channel opens and fast Na+ channel inactivates
phase 2 - plateau phase, large increase in slow inward gCa++ through long lasting ltype Ca+ channels delays repolarization(maintains depol). This happens with membrane potential is -40mV. Blocked by verapamil, diltiazema nd nifedipine. Balanced by K+ outflow through transient outward (lto) and rapid delayd rectifier (lKr) channels
phase 3 - repolarzation when gK+ increases (through IKr, Lto and inward rectifier (Ik1) channels) and gCa++ decreases.
Na channel inactive until half was through phase 3 (absolute refractive period 250ms), then more H gates open so Na permeability increses Na+ reopens at -50 and an appropriate stimulus can cause another action potential (relative refractory period 50ms)
what happens if fast Na chennels are blocked or inactivated by slow deplarization
phase 0 less steep and ap has lower amplitude, depolarization happens through slow inward Ca+ chennels (Ltype) - slow response ap’s
PO 1.43 ionic basis of automaticity and normal cardiac excitation
Pacemaker action potentials
DIfferente because:
- no true resting potential but regular spontaneous ap’s
- depolarzation due to slow inward Ca++ through L type Ca channels instead of fast Na+ (Na+ inactivate as cell more depolarized which closes the h gate)
- no inward K rectifiers so less stable resting membrane potential RMP
- HCN channels responsible for funny current
- Less negative RMP (-60mV) and threshold (-40mv)
- No plateau in phase 2
SA node ap 150ms. myocyte is 250ms
o pacemaker cells are in sinoatrial node (SAN), atrioventricular node (AVN) and purkinje cells (PC)
o rate of automaticity faster in SAN so its primary, others secondary
3 phases:
phase 0 - rapid depolarzaion due to increased gCa++ through L type Ca channels that open at threshold -40mV. gK decreases, funny channel and transient Ca++ channel closes
phase 3 - repolarzation, voltage operated delayed rectifer inward K+ channels open so gK+ increases, Ca++ channels close. Ends at -65mV when K+ channels closes again
phase 4 – spontaneous, diastolic, depolarization leading to subsequent generation of new action potential. Due to
• gK declining
• a ‘pacemaker/funny’ current (If, slow inward movement of Na)
• increase in gCa++ through transient t type channels which open briefly at -50mV, not blocked by verap/diltia,
• Long L type Ca++ opens and soon threshold reached
PO 1.43
ionic basis of abnormal cardiac excitation
- if SA node becomes depressed or its ap doesn’t reach secondary pacemakers, overdrive suprrsion ceases and new pacemaker is the ectopic foci but his is slow and get decreased HR and CO
- afterdepolarization - Non pacemaker cells may undergo spontaneous depolariztion in phase 3 or early phase 4 triggering abnormal action potential, if large enough can trigger self sustaining ap’s - tachycardia
early - in phase 3, from slow inward Ca++, happens if ap’s prolonged
delayed - in last phase 3 or phase 4, happens if high intracelluar Ca++ like in ischaemia, dig tox, xs catecholamine stimulation4
- damaged/dysfunctional conduction system (card 19) damages the pathway so ventricles can’t generate pressure and can get arrhythmia (eg if AV node doesn’t slow ap’s from SA node get af of AF, or if ischaemic or receives XS vagal stimulation vent wont contract and rely on latent pm in the ventricle as above)
- ventricular ectopic outside of fast conducting system means ventricular depol relies on slow cell to cell condction between myocytes (0.5m/sec)
- accessory conduction pathways between atria and ventricle alters the sequenc of ventricular depol can can cause SVT
PO 1.43 normal intrinsic automaticity of SA node
o intrinsic automaticity of SA node - regulation
100-110/min but HR 60-200 due to autonomic nerves acting on SA node and other factors like hormones, serum K and Ca, hypoxia, temp and stretch
- Autonomic regulation
o Sympathetic via adrenergic increases cAMP which increases depolarization and HR (pos chronotropy)
• Stimulates funny channel so increases slope of phase 4
• Also lowers phase 0 threshold
o Parasympathetic via cholinergic decreases cAMP hyperpolarizes resting Em, slow HR (neg chronotropy)
• Increases threshold potential
• Decreases phase 4 slope
• Decreases resting Em
- Hormones
o Adrenergic stimulation through Gq
o Thyroxine increases concentration of adrenergic receptors and rate of Ca++ uptake so increased HR and CO for increase basal metabolic rate - Temperature
o Increases the rate of enzymatic processes so increased O2 requirements so increased CO and HR - Serum ion concentration need to add to this
o Serum K+ modulates K channels
o Hypokalaemia – increased excitability, VT, Vf
o Hyperkaleamia – decreased excitability, brady, asystole - Hypoxia leads to bradycardia
types of cardiac ion channels
PO 1.43 factors that may influence cardiac electical activity
how does sympathetic and vagal tone affect SA node
(see also card 5 and 6 of structure and function)
Sympathetic (see also cell structure and function card 6)
- norephinephrine binds to B1 adrenoceptors couple to stimulatory G protein (Gs-protein), this activates adenylyl cyclase and increases cyclic adenosin monophosphate (cAMP) so get increased opening L-type Ca++ channel and increased If (slow Na+ channels) so rate of depol increases
Vagal (see also cell structure and function card 7)
- Acetylcholine released at Sa node binds to M2 and decreases cAMP via inhibiotry G protein (Gi-protein)
- Acetylcholine may also increase cyclic guanosine monophosphate (cGMP) through nitric oxide (NO - cGMP) pathway which inactivates L-type Ca chennels
- Acetylcholine also activates KaCh - special type of K channel that hyperpolarizes the cell by increasing K conductance
PO 1.43 factors that may influence electrical cardiac activty
mechanisms that affect SA node firing rate
- catecholamines epinphrine work like norepinephrine
- hypokaleamia increases rate of phase 4 depol because decreased K conductance
- hypoxia causes depolarization abolishing pacemaker activity
- digitalis increases parasympathetic activity and inhibits the sarcolemmal Na+/K+ ATPase so get deoplarization and brady
PO 1.43 normal cardiac excitation, correlation of mechanical with ionic/electric
electrical conduction in the heart - describe the pathway that allows rapid, organized, near synchornous depolarization and contraaction of ventricular myocytes to generate ventricular pressure
SA node ap propagates cell to cell.
Cardiac cells connected by low resistance gap junctions at the intercalated disks, so when one depolarizes the positive ionic current spreads to the next
As it depolarizes the atrial muscle it commences excitation-contraction coupling (PO 1.44)
ap spreads between myocytes AND through internodal tracts of atria(specialised conducting pathways)
atria separated from ventricle by non conducting tissue, ap enters ventricle through Atrioventricular node in inferior posterior interatrial septem which slows the impulse (allows complete atrial depol, contraction and emptying and limits frequency of impulse)
then to bundle of HIS, left and right bundle branches - very fast
then purkinje fibers which connect with ventricular myocytes even faster
ventricular myocytes depolarize and contract
PO 1.43 normal cardiac excitation - speed of conducting pathways
PO 1.43 factors that may influence electrical cardiac activity
regulation of conduction velocity
intrinsic and extrinsic factors
Intrinsic
- electrical resistance between cells and nature of the ap. if increased fast Na+ channels, depol happens faster eg. hypoxia decreases these channels so decreased conduction
- in AV nodal cells change in Ca conduction changes rate
Extrinsic
- sympathetic, norephinephrine binds to B1 adrenoceptors and increases conduction velocity - BB blocks this
- parasympathetic, decreases conduction by acetylcholine on M2
PO 1.43 physiological basis of the ECG in normal and abnormal state
P wave - atrial depolarization, .08 to .1 second (repol happens in ventricular depol)
Flat after P - impulse travelling in AV node (slow conduction)
PR interval - from onset of P to beginning of QRS, .12 - .2 secs, time between onset of atrial depol and ventric depol. > .2 seconds means conduction defect in AV node (1st degree HB)
QRS - ventricular depol, .06 - .1 (happens rapidly), > .1 is impaired ventricular conduction (BBB, aberrant conduction, ectopic)
ST - entire ventricle depolarized, = plateau phase of ventricular ap. if up or down its due to non unifrm membrane potentials in ventricular cells
t wave - ventricular repolarization (phase 3 of ap)
QT - ventricular depol and repol, lasts the duration of ventricular ap’s, .2 - .4 (shorter if high heart rate). long QT can make susceptible to arrhythmia. QTc assesses this independant of HR, normal is < .44
PO 1.43
ecg pic and interpretation of pathological ecg
rythem strip II - sinus rythem, SA node controls rythem, 60-100bpm
brady - normal resting high vagal tone, depressed SA node function
tachy - normal is exercise/excitment
AF - high atrial rate, not all conducted through AV
af - depol arises from site other than SA node so no p wave, AV node limits ventricular rate so still have time for filling
AV nodal block - depressed impulse conduction
1st degree - delayed conduction through AV node, > .2sec
2nd degree - AV node doesn’t conduct every impulse
3rd degree - none conducted, ventricle depolarizes from an ectopic junction so its slow (AV node and bundle of HIs 50-60bpm, purkinje 30-40bpm), QRS will be abnormal and wide
VT - usually due to reentry cicuits from abnormal impulse conduction in the ventricle or a rapid ectopic pacemaker site
VF - can happen from VT as can’t fill, unco-ordinated depolarization, can’t see QRS
premature depolarizations - early p or QRS that is odd shape
how ecg records p wave
p wave is atrial depolarizing, peak is when left side has but right side hasn’t yet, back to isoelectric line is when whole thing has (so no potential difference exists between the electrodes). repolarization starts where depol started so if could see atrial repol ud get a negative deflection
In reality many depol waves emerge from SA node and go in many directions, the mean electrical vector is the summation of all of them, pos if towards pos electrode, neg if away and no change if perpendicular
