Transcript for:
Resumen de la Acetilcolina

Acetylcholine is a neurotransmitter that is widely distributed throughout our body, it is responsible for the interaction between neurons in various regions of the central nervous system, for example, in the cortex, basal ganglia, hippocampus, amygdala, midbrain, brainstem, reticular activating system and the spinal cord. diffuse, also participates in the autonomic nervous system, for example, in pre and post ganglionic neurons, also participates in the communication between neurons and glands and, between neurons and voluntary and involuntary muscles, that is, it allows the communication of motor neurons with skeletal muscle, with cardiac muscle as well, and smooth muscle. synaptic terminal, its precursors are, as its name indicates, the acetyl coenzyme that is synthesized from glucose and is used in multiple enzymatic pathways and, also, choline, which is obtained through the diet. The reaction is catalyzed by choline acetyl transferase, once synthesized in the cytoplasm of the synaptic terminal it is transported into the vesicles, thanks to a hydrogen acetylcholine exchanger, called a vesicular transporter. The vesicles filled with acetylcholine fuse with the presynaptic membrane so that it can bind to the receptor with the postsynaptic neuron, the postsynaptic actions of acetylcholine end due to the action of a hydrolytic enzyme, which can be in the cleft or, in the membrane in the postsynaptic membrane, and is called acetylcholinesterase. This hydrolyzes acetylcholine into acetate and choline, now the choline is recovered by the presynaptic neuron by being transported back to the synaptic terminal by a sodium-dependent cotransporter, which is shown here enlarged to be appreciated in the animation, this allows it to be used in the synthesis of more acetylcholine again. All neurons that carry out this process are called cholinergic neurons. Acetylcholine carries out its actions by binding to its receptor, there being two large groups, the ionic channels regulated by acetylcholine and the G protein-coupled receptors activated by acetylcholine which, as we saw previously, are ionotropic and metabotropic receptors respectively. The acetylcholine-regulated ion channel allows the passage of cations, although it is not completely selective, it allows the passage of sodium inwards and potassium outwards, with the entry of sodium predominating more than the exit of potassium, this allows the response of the postsynaptic neuron to be excitatory, since the membrane is depolarized and facilitates the membrane potential to approach the threshold power. This channel is more commonly known as the nicotinic receptor, since nicotine is the one that is activated by the receptor. Acetylcholine-gated ion channels are composed of 5 subunits, there are different types: alpha, beta, gamma, delta and epsilon. To date, 10 different alpha subunits, 4 beta subunits, and the gamma, delta, and epsilon units are known. The transmembrane domains of the 5 subunits form a regulated channel with a central pore that crosses the membrane, the different arrangements of these units give rise to the different subtypes of channels and, in general, two alpha subunits are always present and, it is precisely in the alpha subunits where there is a binding site for the neurotransmitter to bind to the channel, this suggests that generally two molecules of acetylcholine are required to bind to the channel, to make it open, going from the closed to the open state, in which the ions can thus pass through the pore. In skeletal muscle, varying in the arrangement of their units, they are generally 5, although this number can vary between 3 and 5 units to form a functional channel, in this way they have been classified into neuronal type and muscular type. Some of these receptors have seven helical domains that cross the membrane and, in the intracellular region, they have a G protein binding site, as we saw previously, it is a metabotropic receptor, and this receptor is most frequently known. There are five subtypes of G protein-coupled receptors activated by acetylcholine and are called M1 to M5, these couple to different types of G proteins thus causing a variety of responses in postsynaptic neurons, as its name implies, in the presence of acetylcholine the receptor is activated and carries out its effects thanks to the activation of the G protein, the expression of the different subtypes in the neurons of different regions of the brain allows them to act in some as inhibitors, for example, in the neurons of the striatum, and in others as excitatory, such as, for example, in the neurons of the hippocampus, they achieve this because the final effect of the signaling pathway is the opening or closing of potassium channels. Another site where the acetylcholine- activated G protein-coupled receptor is expressed is in the heart, the M2 receptor; the smooth muscle of the bronchi, the M3 receptor; the smooth muscle of the iris and we can also find it in some glands, some examples of substances that interact with these receptors are atropine, scopolamine and ipratopium. It is also important to mention that organophosphates and the nerve agent sarin allow acetylcholine to accumulate in synapses, causing the neuron to depolarize, which ultimately causes, among many other things, neuromuscular paralysis with extremely serious consequences. As we can see, the role of a neurotransmitter such as acetylcholine is of great importance for our organisms, the different types of receptors and their subtypes allow a very wide variety of responses, both in neurons and in the