School of Medicine

University of Washington School of Medicine
CVANS: The Structure Function

HUBIO 543
UW Restricted

CVANS MODULE

spacer

The Heart: an important ANS effector

The heart is an important example of an organ in which dual innervation by the autonomic nervous system usually produces opposite effects. Supraventricular sites of action are innervated by both parasympathetic and sympathetic fibers. The ventricles are innervated by the sympathetic fibers, but there is little functional innervation by parasympathetic fibers. Sympathetic stimulation increases automaticity and contractility in essentially all parts of the heart.

In the SA node, the vagal transmitter (ACh) and other muscarinic agonists inhibit automaticity. This effect is blocked by high doses of atropine. The effects of ACh on the SA node are mediated by an increase in potassium permeability. This promotes hyperpolarization of the SA nodal cells and less rapid phase four spontaneous depolarization.

ACh and other muscarinic agonists slow or block AV nodal conduction. They decrease AV nodal automaticity and increase AV nodal refractory period; all of these effects blocked by atropine. As in other supraventricular cells, the effects of ACh on the AV node are mediated by an increase in potassium conductance. NE and other beta1 agonists accelerate or improve AV nodal conduction. They decrease its refractory period; all these effects are blocked by propranolol. Nodal cells are dependent on calcium channels for conduction of impulses so agents that modify the activity of calcium channels (catecholamines or their antagonists or calcium channel blockers) can have profound effects on cardiac rhythms.

In the atrium, ACh and other muscarinic agonists decrease atrial refractory period and decrease contractility. These effects are blocked by atropine. These effects are all mediated by an increase in membrane permeability to potassium. Increased potassium conductance promotes more rapid repolarization, a shorter action potential duration, less activation of calcium channels, decreased contractility and a shorter refractory period. In the atrium, NE and other beta1 agonists increase automaticity and contractility. These effects are blocked by propranolol. The effects are mediated, at least in part by increased calcium permeability.

In humans, atropine unexpectedly causes bradycardia at low doses. At high doses it causes tachycardia as expected. This is because atropine, at low concentrations, exerts a selective inhibitory effect on presynaptic muscarinic receptors. If one antagonizes the presynaptic autoreceptors, then one may increase the release of ACh. At higher concentrations of atropine, postsynaptic receptors are also blocked and tachycardia is seen. As Gilda Radner said: "It's always something..."

The sympathetic transmitter NE and other beta1 agonists increase SA nodal automaticity. This effect is blocked by propranolol. The effects of NE on the SA node are mediated by increased calcium permeability and more rapid phase four spontaneous depolarization.

View larger image

Ventricular sites in the heart are sympathetically innervated. Vagal innervation of ventricular muscle is sparse and is usually thought of as having minor functional significance. On the other hand, it can be shown that vagal activation can reduce the effectiveness of sympathetic activation, presumably via pre-junctional inhibition of NE release. Activation of beta receptors in ventricular cells increases both automaticity and contractility. A major important effect of sympathetic stimulation is the positive inotropic effect exerted on all myocardial cells. This is seen as an increase in the position of the 'Starling curve' at all muscle lengths.