The neuronal control of Heart Rate

The heart rate is primarily determined by the effects of the autonomic nervous system on the pacemaker cells in the SA node.  The SA node usually fires 70 action potentials per minute (70bpm) without any input from the ANS.

Parasympathetic innervation

• Parasympathetic innervation to the heart is supplied by the vagus nerve.  NB the vagus nerve only really innervates the atria (SA node and AV node), not the ventricles
• It acts to slow the heart rate via the release of acetylcholine that acts by:
  • inhibiting activity of the cAMP pathway via muscarinic inhibitory G-protein receptor binding
    • cAMP directly binds to the ‘funny’ sodium channels that are found in the pacemaker cells to increase their permeability; therefore ACh decreases membrane permeability to sodium
    • a similar effect occurs with T-type calcium channels
      • Both of these slow the rate of depolarisation (by slowing the movement of those ions into the cell and calcium)
  • increasing the permeability to potassium by opening ACh-regulated potassium channels (via the action of G-protein coupling).  This affects the pacemaker potential by
    • reducing the resting potential (more K+ ions leave the cell so membrane is more negative).  This means the pacemaker potential will take longer to reach threshold
    • slowing the rate of depolarisation (more K+ channels need to close during pacemaker depolarisation)
    • decreasing the excitation of the AV-node (again by reducing the resting potential)- this prolongs the AV nodal delay that occurs between contraction of the atria and contraction of the ventricles

Parasympathetic innervation also shortens the strength of contraction by shortening the plateau phase of the myocyte action potential.  This is brought about by closure of calcium channels mentioned above, that usually act to maintain depolarisation.

Sympathetic innervation

• Opposite to the parasympathetic effect, noradrenaline acts on β1-adrenoceptor, activating a stimulatory-G-protein mediated rise in cAMP activity, opening the funny sodium and T-Type calcium channels.
  • This shortens the time taken for the pacemaker potential to reach threshold- increasing the number of APs and thus heart rate
  • It also reduces the AV-nodal delay and increases the speed at which the AP spreads
• Sympathetic innervation covers the whole heart (not just the atria), and will also increase the contractility of the heart, by prolonging the opening of the L-type calcium channels used in the myocyte potentialtoo, to increase the force of the heart.
  • It also speeds up the relaxation of the myocytes by enhancing the active Ca2+ pump in the sarcoplasmic reticulum that removes calcium from the cytosol.  This means that the heart will be more efficient in filling as well as emptying.