Biological Membranes. How Do Neurons Transmit Informa3on? Important parts of the process: 1/24/11

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1 How Do Neurons Transmit Informa3on? Important parts of the process: Biological Membranes The membrane of a neuron is a lipid bilayer. The membrane is semi- permeable - this is cri3cal for producing a difference in poten3al (electrical charge) across the membrane This poten3al difference is produced by ions Ca3ons: posi3vely charged ions (ex. Sodium = Na+, Potassium = K+) Anions: nega3vely charged ions (ex. Chloride = Cl- ) 1

2 Biological Membranes The neuronal membrane has proteins embedded in it: Ion Channels (channel proteins = doorways): allow selected ions to pass in and out of a cell (ex. Na+, K+, Ca++, Cl- ) Receptors: site where neurotransmiper binds, causing an immediate (ion channels open) or delayed (intracellular signaling is ac3vated as with a signal protein) effect Ac3ve transporters: pull certain substances into the cell (ex. glucose, reuptake of neuro- transmipers) The Res3ng Membrane Poten3al Neuron at Rest Membrane Poten3al the difference in electrical charge between the inside and outside of a membrane Res3ng Membrane Poten3al In the res3ng state: more Na + and Cl - ions are outside more K + ions and nega3vely charged proteins are on the inside Allyn & Bacon 2

3 The Res3ng Membrane Poten3al It s between - 60 and - 70mV for most neurons The inside of the neuron is nega3ve rela3ve to the outside Forces That Maintain the Res3ng Membrane Poten3al: Concentra3on Gradient: Na+ more concentrated outside the cell, tends to drive it into the cell. What about K +? Electrical gradient: more posi3ve charge outside the cell tends to drive Na + into the cell. What about K +? Worth Publishers Allyn & Bacon 3

4 Forces That Maintain the Res3ng Membrane Poten3al: Differen3al (selec3ve permeability): In res3ng neurons, K + and Cl - ions pass through the membrane easily, Na + with difficulty, and proteins - not at all. Sodium- potassium pumps (use cellular energy): 3 Na + ions are pumped out for every 2 K + ions pumped in. Worth Publishers Allyn & Bacon Passive and Ac3ve Forces Maintain the Res3ng Poten3al Passive -There is a small, passive leak of K+ out of the cell (K + 20X more concentrated inside the cell); there are large numbers of negatively charged amino acids/proteins that can t move out of the cell (about 100X more concentrated inside the cell this is a large reserve of negative charge) Active (uses cellular energy) - Sodium-potassium pump actively maintains the unequal distribution of positive ions across the membrane: 3 Na + ions out /2 K + ions in Worth Publishers Allyn & Bacon 4

5 The Res3ng Membrane Poten3al A very nice web- based anima3on showing how this comes about can be found at: hpp://bcs.whfreeman.com/thelifewire/content/chp44/ html (for PC) hpp://bcs.whfreeman.com/thelifewire/content/chp44/4401s.swf (for MAC) Graded Poten3als Neurons release chemicals called neurotransmi+ers when they fire NeurotransmiPers diffuse across the synap3c clebs and bind to receptors on the post- synap3c side Worth Publishers 5

6 Graded Poten3als Excitatory Postsynap3c Poten3als (EPSPs) depolariza3ons (ex to - 68 mv) - increase the likelihood that the neuron will fire Inhibitory Postsynap3c Poten3als (IPSPs) hyperpolariza3ons (ex to - 71 mv)- decrease the likelihood that the neuron will fire Worth Publishers Postsynap3c Poten3als Are Graded Poten3als Their amplitude is propor3onal to the intensity of the input Stronger s3muli produce bigger EPSPs or IPSPs Neurons combine together (integrate) individual poten3als - the total determines whether the neuron will fire an ac3on poten3al Neurons integrate incoming signals in two ways: Over space Over 3me 6

7 Allyn & Bacon Allyn & Bacon 7

8 Postsynap3c Poten3als and Ac3on Poten3als The sum of the postsynap3c poten3als reaching the axon hillock (the axon poten3al trigger- zone) determines whether an ac3on poten3al will occur. Elements of The Ac3on Poten3al Voltage- dependent Ion Channels opened by a change in membrane poten3al Absolute Refractory Period brief period aber ini3a3on of an ac3on poten3al when another one cannot be fired (Na + channels temporarily inac3vated) Rela3ve Refractory Period ac3on poten3al can be fired, but it requires a greater than normal degree of s3mula3on Allyn & Bacon 8

9 The Firing Of An Ac3on Poten3al Is An All- or- none Process The Rate Law: Worth Publishers 9

10 The Ac3on Poten3al The Ac3on Poten3al Another nice web- based anima3on showing how this comes about can be found at: hpp://bcs.whfreeman.com/thelifewire/content/ chp44/ html 10

11 Propaga3on of an Ac3on Poten3al Is a Regenera3ve Process Postsynap3c Poten3als and Ac3on Poten3als Postsynap3c poten3als (PSP) are graded poten3als Their amplitude is propor3onal to the intensity of the input s3mulus and decreases with distance from the source (they are generally decremental) The sum of the postsynap3c poten3als reaching the axon hillock (the axon poten3al trigger- zone) determines whether an ac3on poten3al will occur. Ac3on poten3als are not graded poten3als The size of an ac3on poten3al does not vary with s3mulus intensity, only the rate of firing Ac3on poten3als are non- decremental They arrive at the terminals of the axon the same size that they leb the axon hillock 11

12 Local Anesthe3cs Produce loss of sensa3on in limited area of body Many act by blocking Na + channels, and thus blocking ac3on poten3als in the affected area Examples: Lidocaine (Xylocaine) and Novocain General Anesthe3cs Produce unconsciousness Some decrease brain ac3vity by opening some types of potassium channels wider than usual Thus, when a s3mulus starts to excite a neuron by opening sodium channels, K + ions exit about as fast as the Na+ ions enter, preven3ng most ac3on poten3als Examples: ether and chloroform 12

13 Fun with Fugu? Puffer fish (fugu) is considered a delicacy in Japan Some species contain tetrodotoxin (blocks voltage- sensi3ve sodium channels) Very small amounts can shut down signaling to a fatal degree A recipe for fishy revenge! Copyright 2006, Houghton Mifflin Mechanisms for Increasing the Speed an Ac3on Poten3al Increasing Size of Axon Giant axon of the squid can reach a diameter of 1 mm Insula3ng the Axon Myelina3on 13

14 Saltatory Conduc3on in Myelinated Axons Myelin decreases resistance along the axon, thus conduction in myelinated axons is typically faster than in non-myelinated axons of the same diameter Allyn & Bacon Saltatory Conduc3on in Myelinated Axons Worth Publishers Ions can pass through the axonal membrane only at the nodes of Ranvier Current diminishes as it travels rapidly, but passively along the axon between the nodes of Ranvier, but it is s3ll strong enough to open voltage- gated channels clustered at the next node Ac3on poten3als are ac3vely regenerated at the nodes 14

15 Saltatory Conduc3on in Myelinated Axons Conduc3on along the mylinated sec3on of the axon is extremely rapid The ac3ve regenera3on of the ac3on poten3al at the nodes introduces a slight delay (La3n: saltare to skip or jump ) Saltatory conduc3on is more energy efficient Worth Publishers Synapses: How Neurons Communicate Colored electron micrograph of axon terminals from many neurons forming synapses on a cell body Synthesis, packaging and transport of neurotransmi7er molecules Release of neurotransmi7ers Deac;va;on of neurotransmi7ers Ac;on of neurotransmi7ers at receptor sites Classes of neurotransmi7ers Copyright 2006, Houghton Mifflin 15

16 Synapses: How Neurons Communicate Synthesis, Packaging And Transport Of Neurotransmi7er (NT) Molecules Small- molecules NTs (ex. amino acids, monoamines, acetylcholine) Typically synthesized in synap;c bu7on Packed into small vesicles by bu7on s Golgi Stored in clusters next to the presynap;c memebrane Allyn & Bacon 16

17 Synthesis, Packaging And Transport Of Neurotransmi7er (NT) Molecules Large- molecules NTs - (neuropep;des) synthesized in soma (ex. endorphins) Assembled on ribosomes in the cell body Packaged in larger vesicles by the soma s Golgi Transported by microtubules to terminal bu7ons Stored farther from presynap;c membrane that small- molecule neurotransmi7ers Allyn & Bacon Electron Micrograph: Cross Sec3on Of A Synapse Allyn & Bacon 17

18 Electron Micrograph: Cross Sec3on Of A Synapse Copyright 2006, Houghton Mifflin Electron Micrograph: Cross Sec3on Of A Synapse Allyn & Bacon 18

19 Release of Neurotransmi7ers Release of Neurotransmi7ers Ca++ enters cell Synaptic vesicle Vesicle docks to membrane Vesicle fuses NT released Action potential arrives Ac3on poten3al arrives Voltage- sensi3ve calcium channels open Ca++ enters the presynap3c bupon Induces the docking and fusion of synap3c vesicles to membrane Exocytosis: neurotransmiper is released into the synap3c cleb Worth Publishers 19

20 EXOCYTOSIS Worth Publishers Hal3ng Synap3c Transmission - Deac3va3on of NeurotransmiPers Mechanisms to terminate neurotransmitter action: - Reuptake - Enzymatic Degradation 20

21 RECEPTORS AND RECEPTOR SUBTYPES Any molecule that binds to a receptor is a ligand of that receptor. Thus, neurotransmitors are ligands of their receptors. X X RECEPTORS AND RECEPTOR SUBTYPES Receptors are proteins embedded in the membrane that bind neurotransmipers They are specific for par3cular neurotransmipers: a lock and key arrangement (ex. acetylcholine won t bind to a glutamate receptor) X X 21

22 RECEPTORS AND RECEPTOR SUBTYPES Receptor subtypes: Several different receptor proteins can bind the same neurotransmiper (ex., acetylcholine binds both nico3nic and muscarinic acetylcholine receptors) neurotransmitter Receptor 1 Receptor 2 NeurotransmiPers Can Influence A Postsynap3c Neuron In Fundamentally Different Ways By Binding To Either Ionotropic Or Metabotropic Receptors Ionotropic Receptors Binding of neurotransmiper opens, or closes, an ion channel Metabotropic Receptors Binding of neuro- transmiper ac3vates signal proteins and G proteins G protein subunit breaks off and binds to an ion channel, or s3mulates produc3on of an second messenger 22

23 Major Classes of NeurotransmiPers Small- molecule Neurotransmi7ers Large- molecule (pep;de) Neurotransmi7ers Soluble gases Small- molecule Neurotransmi7ers Monoamines 1. Dopamine - movement, a7en;on, learning, reward - degenera;on of Substan;a Nigra in midbrain = Parkinson s disease (loss of DA) - schizophrenia (too much DA release) 2. Norepinephrine and Epinephrine (Adrenaline) - released by sympathe;c n.s. and adrenals - control alertness/wakefulness; alarm 3. Serotonin - control of ea3ng, sleep, and arousal - inhibits dreaming (LSD blocks serotonin) 23

24 Small- molecule Neurotransmi7ers Acetylcholine contracts skeletal muscles (neuromuscular junc;on) parasympathe;c nervous system Small- molecule Neurotransmi7ers Amino Acids Excitatory amino acids (ex., glutamate, aspartate) excitatory neurotransmi7ers producing EPSPs Inhibitory amino acids 1. Gamma- aminobutyric acid (GABA)» inhibitory neurotransmi7er producing IPSP» degenera;on in basal ganglia 2. Glycine» inhibitory neurotransmi7er» normally inhibits motor neuron ac;vity in spinal cord 24

25 Large- molecule (pep;de) Neurotransmi7ers Very diverse types and func;ons Examples: endorphins (endogenous opiates; pain) cholecystokinin (gut pep3de; food intake) vasopressin (fluid regula3on) Soluble gases Small molecules with very different neurotransmiper characteris3cs Produced in cytoplasm by enzymes and diffuses freely across lipid bilayers to neighboring neurons Examples: Nitric oxide regulates vascular relaxa3on involved in learning and memory Carbon monoxide also regulates vascular relaxa3on regulates peristal3c relaxa3on 25

26 1/24/11 Many Drugs and Toxins Act By Mimicking Or Blocking The Ac3on Of A NeurotransmiPer Copyright Thomson & Wadsworth, 2003 Many Drugs and Toxins Act By Mimicking Or Blocking The Ac3on Of A NeurotransmiPer The tetanus toxin blocks the receptors for the inhibitory neurotransmiper GABA. As a result, the disease causes extreme muscle spasms that may lead to the ripping of muscles and the breaking of bones. 26

27 1/24/11 Many Drugs and Toxins Act By Mimicking Or Blocking The Ac3on Of A NeurotransmiPer The tetanus toxin blocks the receptors for the inhibitory neurotransmiper GABA. As a result, the disease causes extreme muscle spasms that may lead to the ripping of muscles and the breaking of bones. Because spasms occur first in the jaw and neck, tetanus is also sometimes called Lockjaw Many Drugs and Toxins Act By Mimicking Or Blocking The Ac3on Of A NeurotransmiPer There are about 100 cases of tetanus per year in the US There are about a million deaths per year worldwide due to tetanus Even in a well equipped hospital 30-40% die 27

28 1/24/11 Many Drugs and Toxins Act By Mimicking Or Blocking The Ac3on Of A NeurotransmiPer There are about 100 cases of tetanus per year in the US There are about a million deaths per year worldwide due to tetanus Even in a well equipped hospital 30-40% die Interestingly, curare derivates are some times used to treat tetanus 28