The Nicotinic

Acetylcholine Receptor
(nAChR)
Amanda Rossman RN, BSN, SRNA
York College of Pennsylvania/Wellspan Health
Nurse Anesthesia program
 Overview
 Receptor composition
 Structure of the receptor
 How the receptor is activated
• What activates the receptor
• How the ion channel opens
 Types and functions of the receptor
 Why this receptor is important to the practice
of anesthesia
 Locations:
• Peripheral Nervous System
• Central Nervous System
 Types:
• Muscle-type
• Neuronal-type
• Non-neuronal type
 Functions
• Dependent upon location and
http://www.jbc.org/content/283/32.cover-expansion

composition
 SUBUNITS SUBTYPES

 α  α 1-10
 β  β 1-4
 δ
 γ
 ε

Rossman, 2011
http://www.jyi.org/research/re.php?id=88
1. Extracellular domain
- Binding sites

2. Transmembrane domain
- Channel gate

3. Intracellular domain
- Regulates expression

Zouridakis et al., 2009

 1. 2.

3.
http://www.medicine.mcgill.ca/mjm/issues/v05n02/v05p090/v05p090fgr2.htm
Rossman, 2011
http://www.biochem.arizona.edu/classes/bioc462/462a/NOTES/LIPIDS/transport.html
http://physiwiki.wetpaint.com/page/Autonomic+Nervous+System
http://www.frca.co.uk/article.aspx?articleid=100618#
Kalamida et al., 2007 http://www.cnsforum.com/imagebank/item/Rcpt_sys_ACH_dist/default.aspx
 Selective to calcium
 Increases intracellular
calcium by:
• Direct influx
• VOCC
• Release from intracellular
stores

http://www.bath.ac.uk/bio-sci/research/profiles/wonnacott-s.html
  Location
 Endocrine
 Endothelial
 Epithelial
 Immune
 Composition
 Hetero/Homomeric
 All 17 subunit
subtypes

http://www.hindawi.com/journals/mi/2010/642462/fig1/
MEMORY MUSCLE CONTRACTION
 General anesthetics  Inhibits calcium
 Non-competitive permeability of the cell
antagonist
•Local anesthetics

•Non-depolarizing
muscle relaxants

•Depolarizing
muscle relaxants

•Inhalational agents

http://www.medicine.mcgill.ca/mjm/issues/v05n02/v05p090/v05p090fgr2.htm
Rossman, 2011
 Upregulated Downregulated
Receptors Receptors

Diseases Upper/Lower motor Myasthenia Gravis,

neuron lesions, burns, congenital myasthenic
immobilization, syndromes
denervation injuries
Depolarizing muscle
relaxants

Nondepolarizing
muscle relaxants
 Located widely throughout the body and is
involved in numerous bodily functions.
• Muscle, neuronal, and non-neuronal types
 This is the target of many anesthetics that we
will use.
• Muscle contraction and memory
 Understanding of this receptor will
help us to appropriately reach the
anesthetic goals for our patient.
 Arias, H. R., & Bhumireddy, P. (2005). Anesthetics as chemical tools to study the structure
and function of the nicotinic acetycholine receptors. Current Protein and Peptide Science, 6,
451-472.
 Dilger J P 1998 Anesthesia Biological FoundationsDilger, J. P. (1998). Structure and function
of the nicotinic acetylcholine receptor. In T. Yaksh, C. Lynch, W. Zapol, M. Maze, J. Biebuyck,
& L. Saidman (Eds.), Anesthesia Biological Foundations (pp. 221-235). Phildelphia,
Pennsylvania: Lippincott-Raven.
 Gotti, C., Riganti, L., Vailati, S., & Clementi, F. (2006). Brain neuronal nicotinic receptors as
new targets for drug discovery. Current Pharmaceutical Design, 12, 407-428.
 Kalamida, D., Poulas, K., Avramopoulou, V., Fostieri, E., Lagoumintzis, G., Lazaridis,
K.,...Tzartos, S. J. (2007). Muscle and neuronal nicotinic acetylcholine receptors structure,
function, and pathogenicity. FEBS Journal, 274, 3799-3845, doi: 10.1111/j.1742-
4658.2007.05935.x
 Lecchi, M., Hoda, J., Hogg, R., & Bertrand, D. (2010). Cys loop receptors. In J. Kew & C.
Davies (Eds.), Ion channels: From structure to function (pp. 209-221). New York, New York:
OXFORD University Press.
 Lu, Z. and Yu, B. (2007) Role of presynaptic acetylchioline autoreceptors at motor nerve
ending on tetanic and train-of-four fade seen during a nondeploarizing neuromuscular
block. Anesthesiology, 106, 1243
 Miller, N. S., & Harkness, P. C. (2008). Assembly and trafficking of nicotinic acetylcholine
receptors. Molecular Membrane Biology, 25(4), 279-292, doi: 10.1080/09687680802035675
 Miller, R. (2010) Miller’s Anesthesia (ed. 7th). Philadelphia, PA: Churchill livingstone.
 Rossman, A (2011). The physiology of the nicotinic acetylcholine receptor and its
importance3 in the administration of anesthesia. AANA Journal, 79(5), 433-440.
 Shen, J., & Yakel, J. L. (2009). Nicotinic acetylcholine receptor-mediated calcium
signaling in the nervous system. Acta Pharmacologica Sinica, 30(6), 673-680, doi:
10.1038/aps.2009.64
 Taly, A. (2007). Opened by a twist: A gating mechanism for the nicotinic
acetylcholine receptor. European Biophysics Journal, 36, 911-918, doi:
10.1007/s00249-007-0189-4
 . Wang, H., Zhang, Y., & Shi-Tong, L. (2010). The effect of local anesthetics on the
inhibition of the adult muscle-type nicotinic acetylcholine receptors by
nondepolarizing muschle relaxants. European Journal of Pharmacology, 630, 29-
33, doi: 10.1016/j.ejphar.2009.12.028
 Wessler, I., & Kirkpatrick, C. J. (2008). Acetylcholine beyond neurons: The non-
neuronal
cholinergic system in human. British Journal of Pharmacology, 154, 1558-1571,
doi: 10.1038/bjp.2008.185
 Xu, Y., Luo, X., Shen, J., Zhu, W., Chen, K., & Jiang, H. (2006). Molecular dynamics
of nicotinic acetylcholine receptor correlating biological funcions. Current Protein
and Peptide Science, 7, 195-200.
 Zouridakis, M., Zisimopoulou, P., Poulas, K., & Tzartos, S. J. (2009). Recent
advances in understanding the structure of the nicotinic acetylcholine receptors.
IUBMB Life, 61(4), 407-423, doi: 10.1002/inb.170