3- ACh Flashcards
Faciltators
Don’t require energy
Highly selective
i.e. glucose
Cant concentrate molecules between regions
Primary Transporters
Uses ATP directly
Can transport in different directions
Secondar Transporters
Antiporter/Symporter
Derives energy from an existing gradient
NT Classification Criteria
Synthesis in neuron and present in nerve terminal
Fast release from electrically stimulated neurons
Has mechanism for terminating action of released NT
Exogenous application of target neurons mimics action see in vivo
Existence of specific receptors
VAChT
Vesicular ACh Transporter
ANtiporter
ACh coupled with proton efflux
nAChR Subunits
Pentameric
Each subunit has 4 TM domains
N and C terminus are located extracellularly
Muscle nAChR
ACH binds at α and delta/epsilon subunit interface
Neuronal nAChR
ACH binds at α and beta interface, or 2 α subunits for A7 receptors
A7 Subunit
Allows for Ca influx if present
Contribute to synaptic plasticity (LTP) and brain developmetn
A7 and Brain Development
Switches GABA from excitatory and inhibitory in early development
Distribution of nAChR in Brain
A4 and B2 in cortex, thalamus, DA neurons
A7 in HPC (L/M)
A3 Subunit
Only subunit that is essential for survival
Homozygous a3 null mice die within first week of birth because of defect in autonomic control of physiological processes
Nictotine Replacement Therapy
Associated with 2 fold increased abstinence rates than palcebo
Bupropion Therapy (Smoking)
Antidepressant
Doubles quit rates compared to placebo
Varenicline (Chantix)
Partial agonist of alpha4beta2 receptors
Reduces rewarding value of cigrarette, decreases withdrawal symptoms
Side effects- increased suicidal thoughts
Psychosis
Difficulty establishing what is real and not
Disordered thinking, speak, hallucinations, delusions
Psychosis and Nicotine
Rates of cigarette smoking 2-3 time higher in those with psychiatric disorders
Heavy smoking, severe nicotine dependence
Reverse Causation
Intensity of smoking in those with psychotic disorder is secondary to illness itself
Medication to alleviate effects of illness can result in nicotine dependence
Shared Liability
Psychotic disorders and cigarette smoking share genetic liability
Confounder
Tobacco smoking associated with oter risk factors
Gateway to other factors that cause psychosis (environmental factors, illicit substance use)
Causal Effect
Possibility that tobacco smoking might be causally related to the risk of psychosis
mAChR and SCZ
Decreased M1 and M4 in PFC, HPC, striatum (basal ganglia)
M1 C267A Gene
Polymorphism associated with PFC dysfunfunction
mAChR and PD
Degeneration of inhibitory DA in substantia nigra causes PD (too much excitatory cholinergic connections of basal ganglia (striatum))
