Acetylcholine receptors

The effects of acetylcholine are mediated by 2 different receptor types:

• Muscarinic receptors
• nicotine receptors

Receptor and ion channel are part of the same protein complex. This is embedded in the cell membrane and consists of 5 subunits that enclose a central pore(ion channel). The binding sites for the endogenous agonist (see figure for a nicotinic acetylcholine receptor) are located extracellularly on one of the channel units. The nicotinic acetylcholine receptor increases the conductivity for Na+ and K+ ions.

Muscarinic receptors (named after an alkaloid of the fly agaric, Amanita muscaria): This type of receptor is a G-protein coupled receptor (metatropic receptors) which can be stimulated by the fungal toxin muscarin. Muscarinic receptors are also called "muscarinic acetylcholine receptors". Muscarinic receptors are divided into 5 subtypes (M1 - M5 receptors):

• M1 -receptors: They have exclusively neuronal functions
• M2 receptors: They are mainly found on heart muscle cells and on smooth muscle cells. On pacemaker cells of the right atrium, activation of this type of receptor leads to a shortening of the G1 protein-regulated action potential duration of the GIRGK channels and thus to a negatively inotropic effect.
• M3 receptors: They are mainly expressed on smooth muscle cells, exocrine gland cells and arterial vascular endothelia. Their presence on the vascular endothelium is a peculiarity in that vessels lack prasympathetic innervation.
• M4 receptors and M5 receptors: Their physiological significance is largely unknown. They are mainly expressed in the CNS.

Nicotine receptors: Nicotine receptors (nicotinic acetylcholine receptors) are receptors that can be stimulated by nicotine. The nicotine effect is mediated by this type of receptor. They are ion channel receptors. 2 subtypes of the nicotine receptor are known:

• NM-receptors: the index stands for "muscular type". They consist of several subunits (2 alpha1, one beta1, gamma, delta, epsilon subunit each) of which 5 always form the receptor channel. With this receptor type, the depolarization of the muscle cell proceeds slowly (end plate potential). An action potential of the muscle cell only occurs when the threshold potential for the fast, voltage-dependent Na+ channels is exceeded.
• NN receptors: the index stands for "neuronal type". There are numerous variants of these receptors, which are found in autonomous ganglia (transmission of excitation), in the adrenal medulla (nor-) adrenaline release and in the CNS (activation of the mesolimbic dopaminergic reward pathway, important role in thought and learning processes). These are ion channel receptors with high conductivity for Na+ and K+ ions.

1. Bernardi CC et al (2010) Amplification and deletion of the ACHE and BCHE cholinesterase genes in sporadic breast cancer. Cancer Geneet Cytogenet 197:158-65.
2. Gertsch M (2008) The ECG: At a glance and in detail. Springer Medizin Verlag 400
3. Gülker H et al (1998) Guidelines for the therapy of cardiac arrhythmias. Walter de Gruyter Publisher 31 - 31
4. Greenfield S (1996) Non-classical actions of cholinesterases: role in cellular differentiation, tumorigenesis and Alzheimer's disease. Neurochem Int 28:485-490.