acetylcholine

characteristics of acetylcholine

molecule = present in synaptic vesicles of nerve terminals, molecule mimics actions of nerve stimulation, molecule released after nerve stimulation, synthesized by presynaptic neuron, termination of action to keep signal brief, target receptors mediate action

otto loewi

endogenous chemical transmitter mediated nerve impulses, stimulated vagus nerve of a frog heart and bathed a second in the media. from the first, and the second frog heart slowed down = vagusstoff

how is acetycholine created?

cholinergic neurons create this in the presynaptic terminal from precursors: choline + acetyl coa with enzyme cholinergic acetyl transferase to create ach, choline is transported all throughout the body into high affinity, low efficinecy choline reuptake transporter - HACU, while acetyl coa is genereated from mitochondria, ChAT is made in cell body and transported down the axon

where is acetylcholine stored?

small clear synaptic vesicles in presynaptic terminal

describe the mechanism of which acetylcholine oes into a synaptic vesicle

it is actively transported into a synaptic vesicle = VAChT and Vacuolar type proton atpase, V-ATPase moves hydrogen into the vesicle making it acidic in atp dependent manner, creates proton gradient for VAChT to pump the ach into the vesicle for 2 protons to leave

how is it released? (synaptic cleft)

synaptic vesicles containing ach are released into synaptic cleft through calcium dependent exocytosis, first ap goes down, vgcc opens, calcium binds to synaptotagmin, then vesicles fuses to release NT

how is it released? axon swellings

they can be released from varicosities on axons, in which they release ACh into the ECS for paracrine signaling through diffusion to local neighboring cells

how is it terminated

the enzyme breaks down acetycholine, acetylcholinesterase exists in the cytoplasm of the axon terminal and synaptic cleft, and AChE hydrolyzes ACh and choline recycled back into presynapse through HACU transporters

receptors of ach

ach both ionotropic and metabotropic - ionotropic = nicotinic,metabotropic = muscarinic

nicotinic receptor

Located in NMJ, ganglia in ANS and CNS, binds to ach, nicotine, curare, alpha toxins and other drugs, permeable to sodium and potassium, just postsynaptic

muscarinic receptor

metabotropic, in visceral organs innervated by ANS (cardiac and smooth muscle) and in cns, cna be both inhibitory and excitatory, and they can inhibit adenylyl cyclase, stimulates the increase of ca2+ through plc, and hyperpolarize through potassium channel activation both pre and postsynaptic

describe the function of acetylcholine at the nmj

released by motor neuron at motor endplate onto skeletal muscle cell with nicotinic acetylcholine receptors, then stimulates the muscle cells to promote contraction

describe the pathways the medulla and spinal cord have with the parts of the body

typically for parasympathetic pathways - medulla synapses with skeletal and cardiac muscles and releases ACh, but for sympathetic pathways releases NE from spinal cord, sweat glands are sympathetic yet use ACh, renal vascular smooth muscle uses dopamine, adrenal medula directly synapses with spinal cord and can do both NE and Epi, skeletal muscles use ACh

describe acetylcholine’s role in the ans

ach is the nt released by preganglionic nerve in both pns and sns, main nt responsible for parasym response in visceral organs but also sympathetic response for sweat glands and piloerector muscle

acetylcholine in the cns

only 1% of cns = cholinergic, widespread effect, released by varicosities in cns and diffuse to other places, they are metabotropic, ach = neuromodulator, it is involved with memory function in neocortex and hippocampus, assoc. with alzheimer’s disease