Neurotransmitters & Signaling Part 1: Acetylcholine & Receptors

Neurotransmitters and Signaling: Acetylcholine

Acetylcholine (ACh) is the neurotransmitter used in several locations, mainly:

• Ganglia of the SNS and PNS

• Synapses at the tissues innervated by the PNS

• Synapses at the neuromuscular junction of the somatic nervous system

ACh is produced in the nerve terminal by choline acetyltransferase and released by exocytosis into the synapse where it interacts with nicotinic or muscarinic receptors.

Nicotinic receptors are found on the:

• Autonomic ganglia

• Neuromuscular junction of the somatic nervous system

• CNS

Muscarinic receptors are found primarily in the:

• Effector organs of the parasympathetic nervous system

Neurotransmission of ACh

Stored vesicles of ACh are released when an action potential arrives at the nerve ending.  Voltage-gated calcium channels open in the presynaptic membrane of the cell causing a rise in intracellular calcium.  Increased calcium levels cause the vesicle membranes to fuse with the cell membrane, which results in ACh being released into the synapse.  ACh then binds with muscarinic or nicotinic receptors on the postsynaptic receptor. ACh also provides inhibitory feedback by binding to presynaptic ACh receptors.  ACh is degraded to choline by acetylcholinesterase in the synaptic cleft. Choline is then recycled back into the neuron.  

Muscarinic Receptors

There are at least five types of muscarinic receptors, which are all found in the CNS. Other specific locations based on receptor type include:

• M1 - Gastric, and salivary glands

• M2 - Cardiac, and smooth muscle

• M3 - Gastric, and salivary glands

M1, M3, and M5 receptors (G-protein linked) interact with Gq, which stimulates PLC (phospholipase C) to hydrolyze PI into IP3. 

• IP3 increases release of Ca from the ER and SR.  

• DAG activates protein kinase C (PKC), which results in extracellular calcium to influx into smooth muscle cells. Influx of calcium into smooth muscle cells causes contraction.

M2 and M4 receptors (also G-protein linked) interact with Gi, which inhibits adenylyl cyclase and decreases cAMP levels. Activation of these receptors also increases potassium conductance.  In the heart, this results in hyperpolarization of cardiac cells and decreases HR and contractility.

Nicotinic Receptors

Nicotinic receptors are found in the autonomic ganglia (NG), CNS, and the neuromuscular junction of the somatic nervous system (NM)

Nicotinic receptors activate a ligand-gated ion channel that allows sodium and potassium ions to enter and depolarize the postsynaptic cell.