| Question | Answer |
| What is the heart | A muscular pump that alternated between contraction (systole) and relaxation (diastole)
Depending on activity will give around 3 billion beats in 80 years |
| What is cardiac output and how is it regulated | Pump rate in regulated from 5 l/min (resting) to around 30 l/min (intense exercise)
Regulated by modulation of the strength of contraction and rate of contraction |
| Gross structure of the heart | Sinoatrial node - pacemaker allowing for myogenic activity
Atrioventricular node
Atrioventricular bundle - Bundle of His
Bundle branches
Purkinje fibres
These create a conduction system to allow depolarisation to propagate and the heart to contract |
| Cardiac myocytes | Ventricular - brick like appearance with striations, mono-nucleated to provide the contraction force
Atrial - smaller as less force is needed, still striated
SAN - very thin, no sarcomeric structures, key cells in the pacemaker |
| Ultrastructure of myocardium | The myocardium works as a mechanical and electrical syncytium
Gap junctions allow for electrical coupling
Desmosomes allow for mechanical coupling - made of proteins embedded in plasmalemma that connect in the extracellular space |
| Gap junctions | Make of connexin 43, 6 monomers form a connexon tunnel which spans the membrane projecting into the extracellular space where it connects to connexons of adjacent cells
This allows movement of ions and hormones between myocytes |
| Organisation of contractile filaments | Similar to that of skeletal muscle
Thick filaments - myosin
Thin filaments - actin, tropomyosin, troponins
Mechanism of contraction is also highly similar |
| Starling's law of the heart | The greater the filling of the cardiac chamber the greater individual myocardial fibres are stretched, hence the greater the subsequent force of contraction
Small changes in size of a myocyte will therefor produce large changes in force generated |
| Spread of impulse in the heart | Generated in the SAN, cannot go directly to the ventricles so must pass through the AVN. This ensures the atria contract before the ventricles
Action potential is prolonged, so the muscle fully relaxes before another AP can be generated |
| Different Action Potential shapes | Different myocytes have different Vrest so have different excitability
Shape of the AP is different in different regions
Longest AP is the bundle branches to ensure ventricles relax before another contraction
Extended plateau phase prevents summation |
| Functions of different action potentials | Pacemaker function - myogenic rhythm
Fast/slow conduction to synchronise contraction
Long plateau to maintain refractoriness and avoid high frequency activation |
| Phases of the Action potential in the SAN | Phase 0 - slow upstroke due to Ca2+ (L-type channels)
Phase 3 - repolarisation due to closing of Ca2+ and opening of K+
Phase 4 - electrical diastolic phase. Changes in K+, Ca2+ and HCN channels produce pacemaker activity - degrades resting potential |
| What are HCN channels | Funny current carried by hyperpolarisation-activated cyclic nucleotide channel
Opens on hyperpolarisation at around -65 mV
Allows inwards flow of Na+ to depolarise the membrane until Ca2+ channels open |
| What sets the pacemaker current | Inwards Ca2+ current
De activation of outwards K+ current
Inwards cation current (HCN at negative voltage)
Sodium Calcium exchanger
Background inwards Na+ leak |
| Phases of the action potential in ventricular myocytes | Phase 0-fast upstroke due to Ca and Na
Phase 1-rapid repolarisation due to inactivation of Ca and Na
Phase 2-plateau. Continued entry of Ca or Na ions through channels and exchanger
Phase 3-repolarisation due to K+
Phase 4-electrical diastolic phase |
| Excitation contraction coupling | T-tubules run parallel to the z-lines in dyads with one SR cisternae
Influx of Ca through voltage gated channels bind to the RyR, triggering it to open
The Ca triggers contraction before being taken back up into the SR via SERCA proteins or out the cell |
| The sodium calcium exchanger | This is used to exclude calcium from myocytes following contraction
This is an electrogenic pump as per Ca extruded 3 Na move in leading to a positive inwards flow
The Na/K pump helps to maintain the Na gradient and offset this |
| Action of Ouabain | Inhibits the Na/K pump
Na gradient lost
Ability to remove Ca2+ reduced
Drugs that generate a Ca2+ gradient can help ad it allows passive removal of calcium |
| Evidence for the role of Ca2+ | Adding a Ca2+ dye to a cardiac myocyte reveals a Ca2+ wave on excitation, which moves through the cell allowing for synchronous contraction |
| Relationship between active tension and systolic Ca2+ conc | The rise in [Ca2+] in normal cardiomyocytes during a beat is only large enough to produce a fraction of the intrinsically available strength (50%)
The strength of contraction can be increased by increments of [Ca2+] attained via ionotropic interventions |
| Modulation of cardiac output | Cardiac output = stroke volume x heart rate
Can change frequency of contraction - chronotropy
Can change force of contraction - inotropy |
| Regulation of Chronotropy - Increased heart rate | Noradrenaline binds to beta adrenergic receptors, activating adenylyl cyclase and producing cAMP. This binds to HCN channels to increase open probability and accelerate pacemaker potential decay
Phosphorylation of LTCC and K+ channels also does this |
| Regulation of Chronotropy - Decreased heart rate | Rate decreased by vagus nerve. Ach binds to M2 type receptors which are coupled with Gi proteins. These inhibit activity of adenylyl cyclase so reduces cAMP
This increases time for Vrest decay, repolarisation and depolarisation |
| Regulation of inotropy - hormones | Sympathetic nerves innervate ventricular myocytes. Noradrenaline activates adenylyl cyclase
PKa phosphorylates Ca channels to increase Ca release.
Phosphorylates PLB to increase Ca reuptake for effective relaxation before next contraction |
| Regulation of inotropy - cell length | Starling's law states that as length of the myocyte increases, force generated increases
Steep change in tension depends on: change in double actin overlap and length dependant change in TpnC Ca affinity
More blood in chambers more forceful contraction |
