Introduction
As discussed in the cholinergic receptors module you completed during the neuroscience course, there are two major subtypes of acetylcholine (cholinergic) receptors: nicotinic and muscarinic receptors. Both nicotinic and muscarinic receptors are present in the central nervous system. In addition, acetylcholine is used as a neurotransmitter by sympathetic and parasympathetic preganglionic neurons, as well as parasympathetic postganglionic neurons.
Acetylcholine differs from most neurotransmitters, in that it is NOT reuptaken into the neuron that released it. Instead, acetylcholine is broken down by an enzyme, acetylcholinesterase, which is present in abundance at cholinergic synapses. The physiology of cholinergic synapses can be altered by administering nicotinic or muscarinic agonists or antagonists, acetylcholinesterase inhibitors that delay the breakdown of acetylcholine, or Botulinum toxins that prevent the release of acetylcholine from presynaptic nerve terminals.
Nicotinic Receptors
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All nicotinic receptors are ionotropic: binding of acetylcholine to the receptor results in the opening of an ion channel. Nicotinic receptors are comprised of 5 subunits, arranged symmetrically around a central pore. At least 12 building blocks and 17 subtypes of nicotinic receptors have been discovered. One of these subtypes is located in autonomic ganglia, where sympathetic or parasympathetic preganglionic neurons synapse with postganglionic neurons. The nicotinic receptor subtype in autonomic ganglia can be affected by specific drugs, as indicated in the table below. Such drugs would globally activate or inactivate both sympathetic and parasympathetic postganglionic neurons. |
| Nicotinic Receptor | Selective Agonist | Selective Antagonist |
| Ganglion Type | Dimethylphenylpiperazinium | Trimetaphan |
Muscarinic Receptors
Unlike nicotinic receptors, muscarinic receptors are metabotropic: they are linked with G proteins. As such, binding of acetylcholine to a muscarinic receptor can elicit a host of effects in the postsynaptic cell.
Muscarinic receptors are located on the peripheral targets of the parasympathetic nervous system (like pacemaker cells of the heart) and in the central nervous system.
There are 5 major subtypes of muscarinic receptors: M1-M5. The most important muscarinic receptor subtype for cardiovascular control is the M2 subtype. This subtype is located in the heart, and is involved in the regulation of heart rate and atrial contractility (note that ventricular contractility is not affected by the parasympathetic nervous system). Binding of agonists to the M2 muscarinic receptor subtype result in an increased K+ conductance and a decreased Ca2+ conductance in the postsynaptic cell.
Are Cholinergic Drugs Used in Cardiology?
Cholinergic neurotransmission plays a major role in regulating the activity of the sympathetic and parasympathetic nervous systems, and thus is profoundly involved in cardiovascular control. Nonetheless, cholinergic drugs are not extensively used in cardiology.
The reason is that drugs that affect cholinergic receptors are not very selective, and have widespread effects.
For example, although there are pharmacological agents that selectively activate or inhibit nicotinic receptors in autonomic ganglia, it would be problematic to globally increase or decrease the activity of all sympathetic and parasympathetic postganglionic neurons in unison. In addition, most muscarinic agonists and antagonists have effects on multiple receptor subtypes. It is possible to elicit more specific effects on the cardiovascular system with drugs that act on adrenergic receptors than on cholinergic receptors.
This is not to say, however, that common drugs affecting cholinergic receptors don't have pronounced effects on the cardiovascular system. A good example is atropine, a muscarinic receptor antagonist that produces a high heart rate along with many other physiological responses (e.g., dry mouth, large pupils, urinary retention, constipation). Atropine might be used as a rescue drug to treat a patient with bradycardia, but has few general uses in cardiology.