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Abstract: Nicotinic acetylcholine receptors
(nAChRs) are a member of ligand-gated ion channels
superfamily. nAChRs consist of non-selective cation
channels responsible for ion flux across cell membrane.
Acetylcholine by acting on nAChR regulates various
cellular processes such as transmitter release, cell
excitability, neuronal integration and influences
physiological functions such as fatigue, anxiety, pain
and cognitive functions. Mutations in these ion channels
lead to pathological disease conditions such as
congenital myasthenia gravis, autosomal dominant
nocturnal frontal lobe epilepsy. In this review, nAChR
ion channel, mutations in the ion channel leading to
disease conditions and their mechanism will be focused.
Acetylcholine (ACh) is synthesised, stored and released
by cholinergic neurons and transduce its signals by
acting on muscarinic (mAChRs) and nicotinic
acetylcholine receptors (nAChRs). nAChRs are present
postsynaptically at the neuromuscular junction and
peripheral autonomic ganglia and at presynaptic sites in
the central nervous system (CNS). ACh by acting on
nicotinic receptors mediates the end plate potential in
muscle or an excitatory postsynaptic potential in
peripheral ganglia. In CNS, it regulates processes such
as transmitter release, cell excitability, neuronal
integration and influence physiological functions such
as fatigue, anxiety, pain and cognitive functions.
nAChRs are pentameric ligand-gated ion channel receptors
and constitute the ion channel with in the receptor.
Dysfunctioning of nAChRs during development, adulthood
or aging can lead to various diseases including muscle
weakness, epilepsy, neurodegenerative disease,
psychiatric disease, nicotine addiction etc. Myasthenia
gravis, a neuromuscular disorder characterized by
weakness and marked fatigability of skeletal muscle, is
caused by an autoimmune response to the ACh receptor at
the postjunctional endplate. However, congenital
myasthenia gravis is a disorder (signs and symptoms
similar to myasthenia gravis) occurring due to mutations
in the nicotinic acetylcholine receptor at the
neuromuscular junction which affect ligand binding and
channel opening kinetics; Autosomal dominant nocturnal
frontal lobe epilepsy (ADNFLE) is an epileptic disorder
which also occurs due to mutations in the presynaptic
neuronal nAChR. In this review, nicotinic acetylcholine
receptor mutations leading to channel disorders, their
mechanisms and therapeutic options are discussed.
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