CHRNA10 (Cholinergic Receptor Nicotinic Alpha Subunit 10) encodes the alpha-10 nicotinic [acetylcholine](/entities/acetylcholine) receptor (nAChR) subunit, a member of the ligand-gated ion channel superfamily. The alpha-10 subunit combines with other subunits (primarily alpha-9) to form functional nAChRs that mediate cholinergic signaling in various tissues, including the inner ear, sensory [neurons](/entities/neurons), and select brain regions.
CHRNA10 (Cholinergic Receptor Nicotinic Alpha Subunit 10) encodes the alpha-10 nicotinic [acetylcholine](/entities/acetylcholine) receptor (nAChR) subunit, a member of the ligand-gated ion channel superfamily. The alpha-10 subunit combines with other subunits (primarily alpha-9) to form functional nAChRs that mediate cholinergic signaling in various tissues, including the inner ear, sensory [neurons](/entities/neurons), and select brain regions.
The alpha-10 subunit primarily forms heteromeric receptors with the alpha-9 subunit (CHRNA9). The α9α10 nAChR is a pentameric ligand-gated ion channel that responds to acetylcholine and other cholinergic agonists. [@lipovsek2012] This receptor subtype is unique among neuronal nAChRs because it is also expressed in non-neuronal tissues and can form calcium-permeable channels.
Pharmacology: Blocked by α-bungarotoxin and other conotoxins
Tissue Distribution
The α9α10 nAChR is expressed in:
Inner ear: Hair cells of the cochlea and vestibular system [@shen2015]
Sensory neurons: Dorsal root ganglia and trigeminal ganglion
Immune cells: Macrophages, T-cells, and dendritic cells
Brain regions: Limited expression in [hippocampus](/brain-regions/hippocampus) and [cortex](/brain-regions/cortex)
Role in Neurodegenerative Diseases
Alzheimer's Disease
While CHRNA10 is not traditionally considered a major player in Alzheimer's disease pathogenesis, emerging evidence suggests roles for cholinergic signaling modulation:
Cholinergic hypofunction is a hallmark of AD, and α9α10 receptors represent a novel therapeutic target for enhancing cholinergic signaling [@ballard2005]
Neuroinflammation: α9α10 nAChRs on immune cells may modulate microglial activation through the cholinergic anti-inflammatory pathway [@rosasballina2009]
Calcium dysregulation: The Ca2+-permeable nature of these receptors may contribute to calcium homeostasis alterations in AD
Parkinson's Disease
Dopaminergic neuron protection: Alpha-10-containing receptors may influence dopaminergic neuron survival in the substantia nigra [@jensen2005]
Levodopa-induced dyskinesias: Cholinergic signaling through nAChRs modulates striatal function and may be relevant to PD treatment complications [@quik2011]
Amyotrophic Lateral Sclerosis (ALS)
Neuromuscular junction: CHRNA10 expression at the neuromuscular junction suggests potential involvement in motor neuron disease [@mordillo2010]
Neuroimmune modulation: The cholinergic anti-inflammatory pathway through α9α10 receptors may affect ALS progression
Therapeutic Implications
Drug Targets
Selective agonists: α9α10-selective agonists for neuroprotection
Positive allosteric modulators (PAMs): Enhance receptor function
Antagonists: May have utility in specific contexts
Clinical Relevance
Hearing loss: α9α10 agonists in development for hearing preservation [@shen2015]
Tinnitus: Modulation of α9α10 receptors may reduce tinnitus
Pain: These receptors are targets for novel analgesics
See Also
[CHRNA9 Gene](/genes/chrna9) — Alpha-9 subunit, primary partner of α10
[Nicotinic Acetylcholine Receptors](/proteins/nicotinic-acetylcholine-receptors) — Receptor family overview