| Question | Answer |
| Cardiac innervation | Parasympathetic via vagus nerve
Sympathetic via postganglionic fibres
Somatic afferent fibres
Intrinsic cardiac nervous system |
| Effects of innervation on the heart | Sympathetic - faster heart rate, faster conduction velocity, stronger contraction and faster relaxation
Parasympathetic - slower heart rate, slower conduction velocity - may innervate ventricles but limited evidence |
| Effects of adrenergic stimulation | Mainly on If, Ica and Ik - these control heart rate
Increases these to give a faster pacemaker, upstroke and recovery |
| Effects of cholinergic stimulation | Can activate K channels, causing hyperpolarisation
Antagonises the sympathetic NS and opens IKACh, reducing heart rate and hyperpolarising membrane potential |
| Ion channels in SAN pace making | Lack of stabilising Ik - more positive and alterable resting potential
Stabilised by IKACh
Early pacemaker current - If
Late pacemaker current - IcaT
Upstroke - IcaL
Recovery - Ik |
| Effect of beta receptors | Beta adrenoreceptor agonists and sympathetic nerve stimulation increase pacemaker and upstroke rate and rate of beating
Reduced RR interval
Steeper phase $ |
| Effect of muscarinic receptors | ACh and parasympathetic nerve stimulation hyperpolarise the membrane potential, decrease pacemaker and upstroke rate and rate of beating
Increased RR interval
Longer phase 4 |
| Positive ionotropic effects of sympathetic nerve stimulation | Increase in sympathetic stimulation increases contraction force independently of frank starling effects |
| Mechanism of beta adrenoreceptor stimulation | Activates adenyl cyclase - cAMP - PKA
Phosphorylates L type calcium channels, phospholamban, Ryr, myofilaments
Increases calcium induced calcium release from stores and inhibits PLB thus enhancing calcium reuptake |
| Ionotropic effects of sympathetic nerve stimulation | cAMP dependent PKA increases Ca entry through LCVGC - increased CICR
Phosphorylation of PLB increases SERCA activity so more Ca in SR - greater release
Kinetics of Ca binding myofilaments altered |
| Evidence that IcaL is altered by PKA | Addition of catalytic subunit of PKA increases IcaL
Current blocked by verapamil - must be IcaL
Therefore beta 1 activation increases calcium transients and contraction |
| Role of protein phosphatase 2A | Activated by muscarinic receptors via RAC1
Dephosphorylates proteins that PKA phosphorylates
A counter balance mechanism
E.g. dephosphorylates L type calcium channels, Ryr, PLB, Connexin 43 and NCX |
| Changed in pressure volume loops during exercise | Frank starling mechanism
Increase in venous return in exercise increases ventricular stretch
This increases stroke volume and cardiac output |
| Roles of pharmacological compounds | Muscarinic agonists - bradycardia and vasodilation
Muscarinic antagonists - tachycardia
Beta adrenoreceptor agonists/antagonists - effects heart rate, conduction velocity and contractility |
| Targets for inotropic agents | Digitalis inhibits NKX
Ca sensitiser alters calcium sensitivity of TnC
PDE inhibitors inhibit phosphodiesterase - increase conc of cAMP |
