PSYC 4309 Ch. 7 Acetylcholine

Acetylcholine

Neurotransmitter involved with the central and peripheral nervous system and synthesized by the cholinergic neurons. It is the target of many of the deadliest neurotoxins.

Acetyl coenzyme A (acetyl CoA)

Precursor necessary for ACh synthesis.

Choline

Precursor necessary for ACh synthesis.

Choline acetyltransferase (ChAT)

Enzyme that catalyzes the synthesis of ACh from acetyl CoA and choline.

Cholinergic

Choline acetyltransferase (ChAT) is only found in ____ neurons.

Vesicular ACh transporter (VAChT)

Vesicle membrane protein that transports ACh into synaptic vesicles.

Vesamicol

Drug that blocks vesicular ACh transporter (VAChT). Decreases ACh released.

intracellular calcium

Neural-dependent release requires ___.

Latrodectus mactans

Black widow spider venom that stimulates ACh release in PNS. Causes abdomen and chest pain, tremors, nausea, vomiting, salivation, and sweating.

Botulinum

Toxin that blocks ACh at neuromuscular junction. Hydrolyzes proteins to prevent vesicle fusion. Causes muscular paralysis.

Acetylcholinesterase (AChE)

Enzyme that controls levels of ACh by breaking it down into choline and acetic acid. Secretes quickly for muscles to relax and more ACh secretion.

Choline transporter

Protein in the membrane of the cholinergic nerve terminal involved with the uptake of choline from the synaptic cleft.

Hemicholinium-3 (HC-3)

Drug that blocks the choline transporter in cholinergic nerve terminals.

Reversible AChE inhibitors

Physostigmine, Neostigmine, Pyridostigmine

Physostigmine

Drug that blocks AChE activity. Can cross the BBB to the CNS. Symptoms of too much ACh include slurred speech, mental confusion, hallucinations, loss of reflexes, convulsions, coma, and death.

Neostigmine

Synthetic analog of the drug physostigmine that cannot cross the BBB. It is used to treat myasthenia gravis due to its ability to block AChE activity in muscle tissue.

Myasthenia gravis

Neuromuscular disorder involving an attack on the muscle cholinergic receptors by one's own immune system.

Pyridostigmine

Synthetic analog of the drug physostigmine that cannot cross the BBB. It is used to treat myasthenia gravis due to its ability to block AChE activity in muscle tissue. Can treat organophosphate poisoning.

Irreversible AChE inhibitors

Organophosphates

Soman

Toxin that causes irreversible inhibition of AChE. It is used as a nerve gas for chemical warfare.

Sarin

Toxin that causes irreversible inhibition of AChE. It is used as a nerve gas for chemical warfare.

Parasympathetic preganglionic neurons

cholinergic

Parasympathetic postganglionic neurons

cholinergic

Sympathetic preganglionic neurons

cholinergic

Sympathetic postganglionic neurons

adrenergic

Basal Forebrain Cholinergic System (BFCS)

Contains medial septal group and nucleus basalis group. Role in cognitive function. Damage to this system contributes to the symptoms of Alzheimer's disease.

Medial septal group

Cholinergic neurons project into hippocampus.

Nucleus basalis group

Cholinergic neurons project into the prefrontal cortex, cingulate cortex, and amygdala.

Laterodorsal Tegmental nucleus (LDTg)

Nuclei within the dorsal lateral pons containing cholinergic neurons that project to the ventral tegmental area (important for stimulating VTA dopamine neurons) and others that project to the brainstem and thalamus (important for behavioral arousal, sensory processing, and inititation of rapid-eye-movement sleep).

Pedunculopontine Tegmental nucleus (PPTg)

Nuclei within the dorsal lateral pons containing cholinergic neurons that project to the substantia nigra (important for stimulating nigral dopamine neurons) and others that project to the brainstem and thalamus (important for behavioral arousal, sensory processing, and inititation of rapid-eye-movement sleep).

Nicotinic receptors

Ionotropic receptors that allow Na+ and Ca2+ influx in neuromuscular junction and postganglionic neurons in the ANS. 5 subunits ((2 α, 1 β, 1 γ & 1 δ)

Desensitization

Altered receptor state characterized by a lack of response to an agonist (ACh or nicotine).

Depolarization Block

Process in which the resting potential across the cell membrane is lost. The neuron cannot be excited until the membrane is repolarized.

Succinylcholine

Chemical similar to ACh that is resistant to metabolism by AChE. It is used as a muscle relaxant during some surgical procedures.

Blockade

Muscle relaxation or paralysis can also be induced by blocking muscle nicotinic receptors, like curare-induced poisoning.

Muscarinic receptors

Metabotropic cholinergic receptors that are selectively stimulated by muscarine. Open K+ channels with a G-protein, causes hyperpolarization. Highly expressed in the neocortex, hippocampus, thalamus, striatum, and basal forebrain.

PKC activation

Muscarinic receptors that activate the phosphoinositide second-messenger system.

PKA inhibition

Muscarinic receptors that inhibit the formation of cyclic adenosine monophosphate (cAMP).

M5 receptors

Cause midbrain LDTg to activate DA neurons in VTA to produce rewarding effects.

M2 receptors

Slows heart rate and reduces contraction of cardiac muscle. (bradycardia)

M3 receptors

Increase gut movements, salivation, sweating, and lacrimation.

Pancreatic β-cells

Innervated by the vagus nerve. M3 receptors stimulate insulin secretion to regulate blood glucose levels.

Parasympathomimetic agents

Drugs that mimics effects of parasympathetic activation. Lacrimation, salivation, sweating, pinpoint pupils, severe abdominal pain, painful diarrhea, cardiovascular collapse, convulsions, coma and death.

Parasympatholytic agents

Drugs that block muscarinic receptors, inhibiting the parasympathetic system. They are deadly at high doses, but at low doses they are used medicinally to dilate pupils, relax airways, counteract cholinergic agonists, and induce drowsiness.

Dry-mouth effect

State characterized by a reduction in saliva production as a result of muscarinic antagonism. Its technical name is xerostomia.

Nicotinic agonist

Nicotine

Nicotinic antagonists

Mecamylamine, Curare

Muscarinic agonists

Pilocarpine, Arecholine

Muscarinic antagonists

Atropine, Benztropine, Scopolamine