Author: Gianpiero Pescarmona
Date: 08/07/2008


Anesthesia, or anaesthesia (see spelling differences; from Greek αν-, an-, "without"; and αἲσθησις, aisthēsis, "sensation"), has traditionally meant the condition of having sensation (including the feeling of pain) blocked or temporarily taken away. This allows patients to undergo surgery and other procedures without the distress and pain they would otherwise experience.
The word was coined by Oliver Wendell Holmes, Sr. in 1846.1 Another definition is a "reversible lack of awareness", whether this is a total lack of awareness (e.g. a general anaesthestic) or a lack of awareness of a part of the body such as a spinal anaesthetic or another nerve block would cause.

Anesthesia differs from analgesia in blocking all sensation, not only pain.


2014-02-07T13:34:27 - Caterina Repetto

Nicotinic acetylcholine receptors

Tortone Francesca e Repetto Caterina

Nicotinic acetylcholine receptors, or nAChRs, are cholinergic receptors that form ligand-gated ion channels in the plasma membranes of certain neurons and on the presynaptic and postsynaptic sides of the neuromuscular junction. They do not use second messengers.
It takes its name from nicotine which is one of its ligands, but its most important ligand is ACh.


Nicotinic receptors, with a molecular mass of 290 kDa, are made up of five subunits, arranged symmetrically around a central pore. In each subunit we can find four transmembrane domains with both the N- and C-terminus which are located extracellularly.
We can classify them into two subtipes: muscle-type nicotinic receptors and neuronal-type nicotinic receptors. In the muscle-type receptors, found at the neuromuscular junction, receptors are either the embryonic form, composed of α1, β1, γ, and δ subunits in a 2:1:1:1 ratio, or the adult form composed of α1, β1, δ, and ε subunits in a 2:1:1:1 ratio. The neuronal subtypes are various homomeric or heteromeric combinations of twelve different nicotinic receptor subunits: α2−α10 and β2−β4. Examples of the neuronal subtypes include: (α4)3(β2)2, (α4)2(β2)3, and (α7)5.

Opening of the nAChR channel pore requires the binding of a chemical messenger.
In muscle-type nAChRs, the acetylcholine binding sites are located at the α and either ε or δ subunits interface (or between two α subunits in the case of homomeric receptors) in the extracellular domain near the N terminus. When an agonist binds to the site, all present subunits undergo a conformational change and the channel is opened and a pore with a diameter of about 0.65 nm opens.
Binding of an agonist stabilises the open and desensitised states. When the channel is open positively charged ions are allowed to move across it: sodium enters the cell and potassium exits. The net flow of positively-charged ions is inward.
The nAChR is a non-selective cation channel: different positively charged ions can cross through. It is permeable to Na+ and K+, but some subunit combinations are also permeable to Ca2, so they can affect the release of other neurotransmitters. The channel usually opens rapidly and tends to remain open until the agonist diffuses away, which usually takes about 1 millisecond.
The nAChR is unable to bind ACh when bound to Curare and analogue toxins which antagonistically bind tightly and noncovalently to nAChRs of skeletal muscles, thereby blocking the action of ACh at the postsynaptic membrane, inhibiting ion flow and leading to paralysis and death.
The activated receptors modify the state of neurons through two main mechanisms:
The movement of cations causes a depolarization of the plasma membrane (which results in an excitatory postsynaptic potential in neurons), but also by the activation of voltage-gated ion channels;
On the other hand, the entry of calcium acts on intracellular cascades leading, for example, to the regulation of the activity of some genes or the release of neurotransmitters.
nAChR function can be modulated by phosphorylation by the activation of second messenger-dependent protein kinases. The phosphorylation of the nAChR by PKA and PKC causes its desensitisation. It has been reported that, after prolonged receptor exposure to the agonist, the agonist itself causes an agonist-induced conformational change in the receptor, resulting in receptor desensitisation.

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