Neural Communication PDF

Neural Communication Overview Learning Objectives The Synapse It is the site of neural communication How do cells communicate with one another? How does communication occur within a single neuron? A healthy neuron has a resting membrane potential (voltage) of between -60 and -80 mV (or -...

Neural Communication Overview Learning Objectives The Synapse It is the site of neural communication How do cells communicate with one another? How does communication occur within a single neuron? A healthy neuron has a resting membrane potential (voltage) of between -60 and -80 mV (or -65 mV or -75 mV) Resting membrane potential: inactive cell ○ If you can’t have a resting membrane potential, you can’t have any other potentials, so the neuron cannot send any signals Neuronal communication is due to ions: Sodium (NA) and Potassium (K) Ions move into or out of the cell, but they do not move freely Neuronal communication is electrical AND chemical ○ Sodium and potassium are positively charged ions (+) ○ As they cross the membrane, they carry that charge with them ○ As they move in/out of the cell, they change the potential (voltage) at the membrane Channels and pumps Plasma membrane is an effective barrier Only certain molecules/ions are permitted to cross the membrane, via channels and pumps Channels: allow passive diffusion (no ATP required) ○ If a channel is open, ions flow through very fast Pumps: actively push ions against their chemical gradient (APT is required; active transport) ○ Pumps have to be open and closed in a mechanistic way, so the flow of ions is slower 1. Protein #1 Sodium-potassium pump: pushing sodium and potassium in a specific way a. Uses ⅔ of all energy (ATP) in the brain b. Pumps 3 ions of sodium out of the cell, and 2 potassium ions into the cell i. 3 positives go out, 2 positives go in = net of -1 inside the cell c. Most sodium is outside the cell, most potassium is inside the cell 2. Protein #2 Potassium “leak” channels a. Passive; no energy required b. Potassium will flow from the inside of the cell where there is more of it, to the outside of the cell, where there is less of it c. Inside of the cell is becoming more and more negative (negatively charged), as potassium flows out d. -70 mV inside the cell Cells are polarized  The resting membrane potential is an equilibrium between chemical forces and electrical forces ○ Chemical force pushes potassium out ○ Electrical force pushes potassium in Under resting conditions, the sodium channel is closed The potassium channel is always open The sodium-potassium pump is always working When a neurotransmitter binds to a receptor, it can have one of two effects (both making the neuron fluctuate in voltage) 1. Depolarize the membrane (from -70 towards 0) a. Makes the cell less polar, since it is moving the voltage towards resting (0) b. Excitatory postsynaptic potential: increases the likelihood of an action potential (when neurons fire) 2. Hyperpolarize the membrane (from -70 to something even more negative) a. Inhibitory postsynaptic potential: decreases the likelihood of action potential i. Inhibiting the neuron from firing (no action potential) Transmission of a post-synaptic potential is graded, rapid, decremental: PSPs travel like an electrical signal along an non-insulated wire ○ Decremental: decaying as they travel Action Potential Generation Axon initial segment Threshold of excitation If the neuron becomes depolarized above its threshold of excitation, than an action potential is generated  The action potential is a massive, brief reversal of the membrane potential (from -70 to +55 mV) An action potential is a all-or-nothing phenomenon ○ It is not graded ○ It is always the same size and shape Frequency of firing: how the nervous system codes for intensity 1. Depolarization phase (RISING PHASE) 2. Repolarization phase 3. Hyperpolarization phase Proteins of the action potential 1. Voltage-gated sodium channels (NAv) a. Open at the threshold of excitation b. Shut off after 1 ms: inactive gate (?)____ c. They are responsible for the rising phase of the action potential 2. Potassium channels (two types) a. The Leak Channels, always open b. Voltage Gated-Potassium Channels: Open during the rising phase of the action potential c. Responsible for the repolarization and hyperpolarization The action potential starts at the initial segment and travels to the terminal: conduction - The action potential looks the same all the way down the axon; it does not decay and is constantly regenerated Conduction in an unmyelinated axon: Voltage-gated sodium channels are present along the axon Unmyelinated axons: NAv everywhere (voltage-gated sodium channels) Conduction speed is limited by the number of voltage-gated sodium channels If you have too few voltage-gated sodium channels, then the action potential decays Axon Myelination: Myelin: acts like insulation Allows the action potential to delay less quickly → which allows for a wider distance between voltage-gated sodium channels Only find voltage gated sodium channels between Nodes of Ranvier Voltage-gated sodium channels are present all along the axon, but only at the Nodes of Ranvier Allows for faster conduction Multiple Sclerosis (MS): related to myelin Disorder that progressively damages and destroys myelin ○ Signal is going to be lost, since conduction fails when myelin is lost 55-75K in Canada (3 new cases/per) Canadians have one of the highest rates of multiple sclerosis in the world Some connection to a herpes virus: Epstein-Barr virus The synapse - receptor types Ionotropic: ○ Ligand-gated ion channels ○ Excitatory (depolarize, Excitatory Postsynaptic Potentials) Sodium comes in ○ Inhibitory (hyperpolarize, Inhibitory Postsynaptic Potentials) Chlorine ○ Fast, transient effect: as soon as they open, the ions rush in and the effect begins Metabotropic ○ Alter cell’s metabolism ○ G-protein coupled receptors (no way for things to travel from inside to outside) - GPCRs G-proteins are signaling molecules ○ Modulatory effect: when the neurotransmitter binds, the receptor changes its formation slightly, causing the G-proteins to break off and start floating around in the cell ○ Modulate signals ○ Slow, longer lasting effect: can results in changes in protein formation/production ○ Causes signal cascades inside the cell Receptor locations Postsynaptic receptors: on the dendrites (or the cell body) usually Presynaptic 1. Autoreceptors a. Allows the cell to monitor its own output; regulating the number of neurotransmitters being released (make sure not too much is being released) b. Inhibitory in nature - causing fewer neurotransmitters to be released during the next time c. Usually metabotropic in nature - slower, longer lasting effect 2. Heteroreceptors a. “Change the volume of the music, but don’t change the music itself” b. Neurons become more sensitized, and when the heteroreceptor is activated, it signals to the neuron to fire more neurotransmitters OR reduce the amount of neurotransmitters released Neurotransmitter clean-up Getting rid of the signal → neurotransmitter cleanup 1. Diffusion: neurotransmitters just float away (rare) a. But this might accidentally cause them to activate other neurons 2. Enzymatic degradation: breaking down of neurotransmitters into component parts (=metabolites) which can no longer bond to the receptor 3. Re-uptake: repackaging of the neurotransmitter for reuse a. Presynaptic i. Get neurotransmitter out of synapse, back into axon, using a specialized protein (transporters) ii. Get neurotransmitter into vesicles, using vesicular transports  iii. Once in vesicles, neurotransmitter can be reused b. Astrocytes i.