Neurophysiology - Cardiac muscle Flashcards
What similarities does cardiac muscle share with skeletal muscle
- Striated appearance
2. Sarcotubular system: T-tubules and sarcoplasmic reticulum (although less developed in cardiac muscle)
What similarities does cardiac muscle have to smooth muscle
- Involuntary control (ANS and Endocrine axes)
2. Cells connected by low resistance gap junctions forming a functional syncytium.
How is the resting membrane established in cardiac muscle cells and how does this differ from neurons?
Neurons: K+ leak channels always open
Cardiac myocytes: K inward rectifying channels which open at negative membrane potentials but close with depolarisation –> K+ diffuses out the cardiac myocytes down its electrochemical gradient resulting in the cell interior becoming negatively charged with respect to the cell exterior.
What is the RMP in the heart
Varies depending on cardiac region
Sino-Atrial node = ± - 50 mV (but unstable)
Atrial myocyte = -70 mV
Purkinje fibre = - 90 mV
Ventricular myocyte = -90 mV
How do cardiac and nerve action potentials differ
- RMP: Cardiac - variable depending on cardiac region (SA -50 mV, Atria -70 mV, Purkinje/Ventricular myocyte -90mV). Nerve - - 70mV
- Duration: Cardiac (ventricular myocyte/purkinje) 200 - 400 ms. Nerve - 1 -2 ms
- Morphology: Atrial myocyte - triagular waveform. Ventricular myocyte prolonged plateau phase.
Nerve - Single spike - The Role of Ca++
- Ca++ influx in cardiac cells prolongs the duration of the action potential –> plateau phase.
- Nerve: Ca++ plays no role
How many phases does the cardiac action potential have - describe what happens in each phase
Draw the cardiac action potential in a ventricular myocyte
Phase 0
- V gated Na channels open
Phase 1
- V gated Na channels close
- Fast V gated K channels transiently open
Phase 2
- Fast V gated K channels close
- Slow V gated L-type Ca channels open
- Slow delayed rectifier K channels open
- —> Plateau
Phase 3
- Slow V gated L-type Ca channels close
- Rapid delayed rectifier K channels open
Phase 4
- Ca, Na and K conductance have returned to resting levels with K conductance exceeding Na and Ca. –> RMP
What are the durations of each phase of the cardiac action potnetial and how do the phases of the cardiac action potential correspond to the ECG waveforms
Phases 0 and 1 have a duration of 1 - 2 ms similar to the AP in a nerve. This corresponds to the QRS complex
Phases 2 duration 200ms and corresponds to the ST segment
Phase 3 duration 50ms and corresponds to T wave
How does the duration of the cardiac action potential vary with heart rate
Increasing heart rate –> decreased duration of cardiac AP
HR = 75 bpm --> ventricular AP lasts 250 ms HR = 200 bpm --> ventricular AP lasts 150 ms
Describe the absolute and relative refractory periods of the cardiac action potential
ARP –> crom phase 1 to half way through phase 3
RRP –> halfway through phase 3 and phase 4.
ARP prevents cardiac tetany which would be incompatible with diastolic filling
What is meant by automaticity
Spontaneous decay of membrane potential of a pacemaker cell.
In the SA node this is spontaneous decay from -60 mV to - 40 mV.
The rate of the decay of membrane potential determines the heart rate
This property of the pacemaker cell is called automaticity
What is the historical name for the physiology of automaticity. Describe the physiology that brings about automaticity
The ‘funny’ current (If)
Slow depolarization of the membrane brought about by intracellular movement of Na ions exceeding the extracellular movement of K ions.
Describe the action potential of pacemaker currents
PHASE 4: Action potential leads to hyperpolarization
–> Hyperpolarization-activated cyclic nucleotide gated channels (HCN) - permeable to both Na and K. Na . K –> gradual depolarization towards threshold
PHASE 4: @ - 50 mV –> T-type Ca channels open –>Ca moves into cells –> enhancing membrane depolarization
PHASE 0: -40 mV is then reached –> Action potential: L-V gated L-Type Ca+ channels open
PHASE 3: L-Type Ca channels close. V gated K channels open –> Repolarisation and then hyperpolarization
PHASE 4…
The cycle repeats
= automaticity
Describe the electrical conducting system in the heart starting at the SA node
SA Node
Internodal pathways
- Anterior (Bachmann)
- Middle (Wenckebach)
- Posterior (Thorel)
AV node
Bundle of His
Left bundle branch
- Left anterior
- Left posterior
Right bundle branch
Purkinje fibres
Cardiac myocytes
- -> intercalated discs between myocytes allow them to contract as one unit or a functional syncytium.
- -> Adjacent to the intercalated discs are gap junctions which allow the AP to pass from one myocyte to the next
Why is the AV node the only place where action potentials from the atria can be conducted to the ventricles
Elsewhere the junction between the ventricles is insulated by the ANNULUS FIBROSIS
What part of the ECG is represented by the delay at the AV node
The PR interval
Draw the graph that demonstrates the cardiac action potential and muscle contraction in the ventricle
Page 254 Chambers
Draw the pacemaker action potential and annotate the graph to explain the physiology
Page 255 Chambers
How is cardiac contraction terminated
Active removal of Ca from the cell
During diastole the IC Ca conc. is extremely low. Achieved via the following mechanisms
- Plasma membrane Ca ATPase pump
- Ca/Na exchanger (3:1. Depends NA/K ATPase)
- SERCA ATPase pump –> uses ATP to sequester Ca into SR
What structures give the heart the property of automaticity
Hyperpolarisation-activated cyclic nucleotide channels (HCN channels)
Describe the effects of the PSNS on the heart
Right vagus supplies SA node
Left vagus supplies AV node
SA node –> pacemaker activity slowed
AV node –> conduction reduced
No affect on contractility
What is the intrinsic rate of the SA node and how is this affected by the PSNS
Intrinsic rate: 90 - 120
Continuous PSNS input to SA node = vagal tone –> HR 60 - 80 bpm
What is the cellular mechanism for vagal tone on the SA node
- Ach released from postganglionic PSNS fibre
- Binds G protein coupled receptor on post synaptic membrane
- G protein activated: Gai and GBy divide
- Gai –> inhibit adenylate cyclase –> decrease IC cAMP –> decreased activation HCN channels –> reduced Na influx and reduced If (funny current) –> reduced heart rate.
- GBy –> Activated inward rectifying K channels –> K efflux –> membrane hyperpolarization –> counteracts pacemaker current –> slows HR
How does the SNS innervate the heart
SNS fibres from T1 - T3 innervate the heart myocardium and conducting system.
These fibres synapse with B1 adrenergic receptors - a G protein coupled receptor –> Increased cAMP IC and Protein kinase A:
- Positive chronotropy
SA node: cAMP opens HCN –> increased Na influx i.e. increased ‘funny current’ –> threshold reached faster - Positive inotropy
Cardiac myocytes: Protein kinase A phosphorylates L-type Ca+ channels –> increased Ca+ influx during plateau phase –> increase IC Ca+ –> increased strength of contraction - Shorter AP duration
Protein kinase A increases opening of delayed rectifier K channels during phase 3 –> shortening repolarization time. - Increased rate of transmission through AV node
Opposite effect of PSNS.
Summarize the PSNS and SNS effect on heart rate with regard to overall mechanism of increased and decreased heart rate
PSNS
- -> Gai–> Reduced cAMP –> slowed HCN channels –> slowed pacemaker potential
- -> GBy –> Protein kinase A–> + Kir –> Hyperpolarization (distant from threshold)
- -> slowed conduction through AV node
SNS
- -> B1 –> Gs –> increased cAMP –> +HCN channels –> faster (steeper) pacemaker potential –> faster HR
- -> B1 –> Gs –> Protein kinase A –> P of L-Type Ca channels –> increase Ca influx –> increased inotropy
- -> B1 –> Gs –> Protein kinase A –> open delayed K rectifier channels (phase 3) –> shortening repolarization time
- -> B1 –> increased rate conduction through AV node
Describe immunological complications associated with local anaesthetics
Allergic: local and systemic
Especially ester local anaesthetics
Cocaine
Procaine
Amethocaine
Describe the mechanism and phases of CNS toxicity with local anaesthetics
- EXCITATORY PHASE
V gated Na channels blocked in inhibitory interneurons first –> tinnitus, circumoral paraesthesia, seizures. - DEPRESSIVE PHASE
V gated Na channels blocked in excitatory interneurons –> coma, respiratory depression
Describe the mechanism for CVS toxicity with local anaesthetics
Local anaesthetics block: Na, K and Ca channels in the heart.
Initial signs: bradycardia / refractory VF
List the following in order of CVS toxicity and explain:
- Lignocaine
- Racemic Bupivacaine
- Levobupivacaine
Most to least toxic
- Racemic bupivacaine (S and R enantiomers present)
- Levobupivacaine (S - bupivacaine)
- Lignocaine
Ion channels are stereospecific and the S-enantiomer, levobupivacaine is less toxic
Bupivacaine is more CVS toxic than other local anaesthetics because of higher affinity for Na channels in the heart and due to the fact that bupivacaine also binds Ca channels preventing Ca release from SR.
Describe the effects of the denervation in the transplanted donor heart
Heart relies on automaticity and Starlings law only
- Loss of vagal tone: HR = 100 bpm
- Loss of CVS reflexes
- Laryngoscopy response lost
- Peritoneal traction response lost
- Anaesthetic drug related fall in SVR is poorly tolerated
(dramatic hypotension if preload is not maintained. - Blunted CVS response to exercise
- HR gradually increases with exercise
- HR gradually decreases with rest
(B1 adrenoreceptors on heart still sensitive to circulating adrenalin released by adrenal glands during exercise)
What is the Bainbridge reflex
Increase heart rate in response to stretch of the atria (increased venous return/preload)
What are the pharmacological implications after heart transplant
- Atropine and glycopyrrolate have no effect
- No PSNS innervation therefore atropine has no M to block
(use isoprenaline B1 agonist) - Adrenalin and noradrenalin have increased effect
- Denervation causes upregulation of B1 adrenergic receptors –> exaggerated response to catecholamines
