Cell Neuro / Modulation

October 7th, 2024 Cell Neuro / Modulation Ionotropic transmission = neurotransmitter binds to a receptor which is associated directly with an ion channel that then opens or closes Metabotropic transmission = neurotransmitter/neuromodulator binds to a receptor, activating a G protein cascade that ultimately results in a change in the open/closed status of ion channels. Neuromodulator effects - Changes the strength of a synapse by altering the effectiveness of a neurotransmitter by keeping a channel open longer or the channel is more likely to open when another signal comes along a.) can change the firing properties of the neuron, can change a cell that normally fires a single action potential into a bursty cell b.) can make a cell more likely to fire by closing potassium channels Some of the more common metabotropic neurotransmitters include - Monoamines = dopamine, norepinephrine, and serotonin - Peptides - 100s of types - Acetylcholine = at muscarine receptors Metabotropic actions may be slower to activate but can last longer than inotropic actions - Can last days or weeks or hours - This can result in permanent changes in synaptic strength by activating transcription of genes Metabotropic receptors can share certain features which include 1.) The same numbe of membranes spanning regions 2.) Carboxyterminand and the aminoterminal on the outside 3.) On the inside is where the G protein can bind Sites on the inside for phosphorylation, this is how the receptor desensitizes after activation STEPS IN METABOTROPIC RESPONSE A. Neurotransmitter bind to the receptor B. The receptor binds to the G protein, G proteins have 3 subunits ( alpha which holds a GDP molecule, beta, and gamma ) C. G protein becomes activated a. There is conformation of G protein b. Alpha loses affinity for GDP- and it now becomes GTP c. Alpha splits from the beta and gamma subunits D. these separated G proteins can do different things such as - Directly opening an ion channel - Activate other proteins like kinases or enzymes E. alpha subunit is a GTPnase and knocks off a P from GTP to make GDP F. G protein reassembles G. Receptor desensitizes by being phosphorylated inside to change its conformation to no longer bind to the neurotransmitter Example of G protein acting on a n ion channel - Ach receptor (muscarinic) in the heart - Here, the beta-gamma subunit activates an ion - Application to a patch-clamped piece of heart muscle membrane of the beta-gamma subunit elicited the same effects as applying Ach - Slows the heart rate by opening potassium channels Typically the active G protein subunits move on to do other things, the alpha can do different things from the gamma May activate the production of cAMP or other 2nd messengers, in some cases cAMP opens or closes a channel but usually it moves along cAMP activates protein kinase A PKA which (with ATP for energy) can phosphorylate proteins Phosphorylated proteins may change confirmation if they are ion channels, this may lead to them opening or closing. Or —------ as in a heart muscle with norepinephrine action on the heart muscle it may make an ion channel more available to open, The Ca2+ channel on muscle is associated with contractions and can increase the strength of connection and moves Vm more (+) so heart rate increases Synaptic gets inactivated Different n.t.s utilize specific enzymes Ach uses acetylcholine esterase AchE Less than Ach can have its effect when it’s released into the cleft, when it is no longer released the AchE can catch up and also free up the receptors to be used again. For monoamines, MAO does sthe job