Ionotropic and Metabotropic Receptors

Slides:



Advertisements
Similar presentations
Synaptic Cleft: Information Transfer
Advertisements

What about communication between neurons?.  presynaptic ending – ◦ portion of the axon conveying information to the next neuron.
Neuronal Transmission
SYNAPSES AND NEURONAL INTEGRATION
Membrane Potential 6-35.
Synaptic Transmission
Synaptic Transmission Chapter 4 Pages Chemical Synapses  Most synapses in the brain are chemical. Electronically coupled gap junction synapses.
Neurotransmitters A. Criteria
Part Fundamentals of Physiology Part II Food, Energy, and Temperature Part III Integrating systems Part IV Movement and Muscle Part V Oxygen, Carbon dioxide,
Transmission across synapses a. Depolarization of presynaptic cell b. Increase in inward gCa ++ via voltage gated Ca ++ channels c. Vesicle migration.
Synapses Figure
A connection that mediates information transfer from one neuron:
Synapse and Neurotransmitter Dr. Shaikh Mujeeb Ahmed Assistant prof. Physiology Al Maarefa College 1 Lecture slides are prepared by Dr.Mohammed Sharique.
Chapter 5 Synaptic Transmission
Synaptic Transmission and Neural Integration
1 Session 5 The Neuron II: Synaptic Transmission PS111: Brain & Behaviour Module 1: Psychobiology.
Additional review Neural synapse Neurotransmitters
PHYSIOLOGY 1 LECTURE 14 SYNAPTIC TRANSMISSION. n Objectives: The student should know –1. The types of synapses, electrical and chemical –2. The structure.
Two types of signal conduction within a single neuron
Communication Within the Nervous System
Neurons Structure and Conduction of a Nerve Impulse.
Nervous System: Part III What Happens at a Synapse?
Lecture Presentation by Lee Ann Frederick University of Texas at Arlington Chapter 12 Neural Tissue © 2015 Pearson Education, Inc. Capítulo 12 Tejido Nervioso.
Neurotransmitters Lecture 13.
NT’s, Receptors and their actions Cholinergic Receptors (receptors that respond to Ach) –Nicotinic –Muscarinic Adrenergic Receptors (receptors that respond.
Essential knowledge 3.E.2 Animals have nervous systems that detect external and internal signals, transmit and integrate information, and produce responses.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Nerve Fiber Classification  Nerve fibers are classified according to:  Diameter.
Neurotransmitters & Receptors Lecture 10. Ligands & Receptors n Ligand l Neurotransmitters (NT) & Drugs n Receptor proteins l Control ion channels n NT.
Announcements Mid term room assignments posted to webpage A – HoS361 (Pavilion) Hoang – LischkaS309 Lishingham - NguiS143 Nguyen – SeguinS128 Sek – ZiaH305.
Functional Human Physiology for the Exercise and Sport Sciences Synaptic Transmission and Neural Integration Jennifer L. Doherty, MS, ATC Department of.
University of Jordan1 Receptors Functions and Signal Transduction- L3 Faisal I. Mohammed, MD, PhD.
Nervous Tissue A. Nervous system divisions B. Functional anatomy of nervous tissue B. Functional anatomy of nervous tissue 1. Neuroglia 1. Neuroglia a.
Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Human Anatomy & Physiology, Sixth Edition Elaine N. Marieb PowerPoint ® Lecture.
CHAPTER 48  NEURONS, SYNAPSES, & SIGNALING 48.1  Neuron organization & Structure I. Intro to information processing A. Processing 1. Sensory input a.
Neurotransmitters & Receptors. Sensory neuron Motor neuron Receptor potentialAction potential Synaptic potential Action potential.
Nervous Tissue Chapter 12. Nervous System Controls and integrates all body activities Basic functions: Sense change Interpret and remember change React.
Neurotransmitters Lesson 13. Neurotransmitters n Chemical messengers l Signal between cells n Released at axon terminal l By action potentials n Metabolism.
Synaptic Transmission and Neural Integration
Copyright © 2010 Pearson Education, Inc. The Synapse A junction that mediates information transfer from one neuron: To another neuron, or To an effector.
Physiology of synapses, interneuronal connections
Sci2 Lect 5 Synaptic Transmission ©Dr Bill Phillips 2002, Dept of Physiology Fast Excitatory Postsynaptic Potentials Ligand gated ion channels Presynaptic.
(1)Graded potentials on the post-synaptic membrane: depolarization and hyperpolarization; ligand-gated mechanisms (2) What happens at a synapse? A.  Transmitter.
Copyright © 2005 Brooks/Cole — Thomson Learning Biology, Seventh Edition Solomon Berg Martin Chapter 39 Neural Signaling.
Neural Tissue: 2.
Neurons: Cellular and Network Properties
Neurons & Nervous Systems. nervous systems connect distant parts of organisms; vary in complexity Figure 44.1.
Neurotransmitters A. Criteria 1. must mimic presynaptic effects if administered exogenously 2. must be released during activity of presynaptic neuron 3.
Nervous system works because information flows from neuron to neuron
Read page on drugs and the brain What 3 major concepts should we study to understand this article further?
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Ch 48 – Neurons, Synapses, and Signaling Neurons transfer information.
Neurons, Synapses, and Signaling
CBNS 106 Review Lecture 2.
Nerve Fiber Classification
Neural transmission. The Reticular theory vs the Synaptic theory.
Neurophysiology II: The Synapse Synapse Defined Space between adjacent neurons! Relays information from one neuron to another! Neuron  Neuron Neuron.
AP Biology Nervous Systems Part 3.  I. Synapses – These are the gaps between neurons or between neuron and effector cells.  A. There are two types of.
Cell to cell communication in the nervous system The synapse Electrical synapse Chemical synapse Role of calcium “neurocrines” Receptors Post-synaptic.
Chapter 2 Structure and functions of cells of the nervous system.
Nerves & signaling Ch 37. I. Nerves =  A. Cells called neurons bundled together in a sheath of connective tissue.
The Synapse A synapse is the functional connection between a neuron and a second cell. The second cell is also a neuron in CNS. In the PNS, the second.
Synaptic transmission
Chapter 8 Synaptic Transmission and Neural Integration
Synapse and Neural Integration
Comparative Vertebrate Physiology
Mind, Brain & Behavior Friday January 31, 2003.
Communication Within the Nervous System
At resting potential Most voltage-gated Na+ and K+ channels are closed, but some K+ channels (not voltage-gated) are open.
12-7 Synapses Synaptic Activity Action potentials (nerve impulses)
A junction that mediates information transfer from one neuron:
Cell to cell communication in the nervous system
Presentation transcript:

Ionotropic and Metabotropic Receptors

Recall the 2 Kinds of Synapses? Electrical 2 neurons linked together by gap junctions Function in nervous system: - rapid communication - bidirectional communication - excitation/inhibition at the same synapse Some between neurons and glia cells Chemical Signal transduction Excitatory Inhibitory Slower communication Unidirectional communication

Recall where chemical synapses are found?

Recall the Chemical Synapse?

Communication Across a Synapse Action Potential Voltage-gated Ca channels open Ca triggers exocytosis Nt diffuses and binds to receptor Response in cell Response is terminated by removing nt from synaptic cleft 6. Degradation Reuptake Diffusion

Signal Transduction at Synapses Rate of the response is due to the mechanism by which the signal is received and transferred at the plasma membrane. Fast responses at ionotropic receptors (channel-linked). Slow responses at metabotropic receptors (G-protein-linked).

Ionotropic Receptors The receptor is a ligand-gated ion channel. Ligand binding directly opens ion channel. Fast action, short latency between nt binding and response. Response is brief.

Ionotropic Receptors 5 subunits form the pore through the membrane. Binding of ligand opens the pore. Ions flow into or out of the cell. Produces EPSP or IPSP (depending on the ion channel). Rapid desensitization (loss of activity) if continuously exposed to nt. Limits postsynaptic responding when presynaptic neurons are highly active for a period of time.

Ionotropic Receptors Sensitization High Ion Flow Low Time, ms, in exposure to neurotransmitter

Ionotropic Receptors Can have multiple binding sites for various neuromodulators. Can enhance or inhibit binding of endogenous ligands. Are good targets for drugs.

Fast Responses at Ionotropic Receptors

Metabotropic Receptors Most common type of receptor. Coupled to G protein. No direct control of ion channels. Second messengers.

Metabotropic Receptors Single subunit with 7 transmembrane spanning domains. Highly conserved across the “receptor superfamily”. Ligand binds in cleft on external face. Ligand binding activates G protein G protein activate various effectors. Sometimes the effectors are the ion channels.

αs αs β γ γ β αs GTP NE + GDP cAMP GDP ATP cAMP i3 loop GTP GDP 3) Binding of i3 to the αs subunit of the Gs protein results in a conformation change in αs, causing GDP to dissociate and GTP to bind. (Click to see animation; click again for next step) 4) The GTP-bound αs subunit dissociates from the β subunit and from the βAR receptor and binds to adenyl cyclase (AC). (Meanwhile, norepinephrine may dissociate from the receptor, but the αs subunit can remain active for many seconds after this dissociation.) (Click to see animation; click again for next step) 2) Binding of NE causes the third intracellular loop (i3) of the receptor to change conformation and bind to the GDP-bound αs subunit of the Gs protein. (Click to see animation; click again for next step) 6) After hydrolysis of GTP to GDP, the αs subunit returns to its original conformation, dissociates from AC (which then becomes inactive), and reforms the trimeric Gs protein complex. (Click to see animation; click again for next slide) 5) Activated adenyl cyclase produces many molecules of cAMP from ATP. (Click to see animation; click again for next step) 1) The ß-adrenergic receptor is a 7-transmembrane spanning protein. A negatively charged Asp residue on the 3rd transmembrane region (TM3), along with other charged, polar residues, allows a positively charged norepinephrine (NE) molecule to bind to the hydrophobic core of the receptor. (Click to see animation; click again for next step) β-adrenergic receptor GTP αs TM1 TM5 TM4 TM3 TM2 N TM7 TM6 Asp - N Extracellular space TM3 TM2 TM4 Asp - TM1 NE + TM5 TM7 TM6 GDP αs AC β γ cAMP γ β AC αs GDP C ATP cAMP i3 loop GTP GDP Gs protein Cytoplasm

Slow Responses at Metabotropic Receptors: Direct G-Protein Coupling

Slow Responses at Metabotropic Receptors: Second Messenger Coupling

Postsynaptic Potential Change in membrane potential in response to neurotransmitter binding to receptor. Can be excitatory or inhibitory: - Excitatory: likely to elicit action potential: Deporalization -Inhibitory: less likely to elicit action potential: Hypoerpolarization Membrane Stabilization

Excitatory Synapses Depolarize postsynaptic cell -Brings membrane potential closer to Threshold by opening or closing ion channels. Channels affected are: - Open Na channels - Close K channels - Open channels that are equally permeable to Na and K Causes depolarization because of the stronger force of Na to flow into the cell Depolarization = EPSP (excitatory postsynaptic potential)

Fast EPSPs

Slow EPSPs

EPSPs are Graded Potentials Higher freq of APs (presynaptic) More neurotransmitter released (presynaptic) More neurotransmitter binds to receptors to open (or close) channels Greater increase (or decrease) ion permeability Greater (or lesser) ion flux Greater depolarization

Inhibitory Synapses Neurotransmitter binds to receptor. Channels for either K or Cl open  hyperpolarizes the cell. If K channels open, then…  K moves out  IPSP (inhibitory postsynaptic potential) If Cl channels open, then either…  Cl moves in  IPSP  Cl stabilizes membrane potential.

Fast Inhibitory Synapses Involving K Channels

IPSPs are Grade Potentials Higher freq of APs (presynaptic) More neurotransmitter released (presynaptic) More neurotransmitter binds to receptors to open (or close) channels Greater increase (or decrease) ion permeability Greater (or lesser) ion flux Greater depolarization

Neural Integration Divergence/convergence Summation The summing of input from various synapses at the axon hillock of the postsynaptic neuron to determine whether the neuron will generate action potentials

Divergence

Convergence

Convergence of Input as a Factor in Summation

Temporal Summation from the same Synapse

Spatial Summation from Different Synapses

Neurotransmitters Acetylcholine Biogenic Amines Amino Acid Neurotransmitters Neuropeptides Autonomic Nervous Sysntem

Acetylcholine Found in the CNS and PNS Most abundant neurotransmitter in PNS. Synthesis - Acetyl CoA + choline  acetylcholine +CoA - Synthesized in cytoplasm of axon terminal - Biosynthetic enzyme: choline acetyltransferase (CAT) Breakdown - Acetylcholine  acetate + choline - Degradation occurs in synaptic cleft - Degradative enzyme: acetylcholinesterase (AchE)

Cholinergic Synapse

Cholinergic Receptors Nicotinic - Ionotropic - Found mostly in the skeletal muscle - Some found in the CNS Muscarinic - Metabotropic - Found mostly in the CNS

Actions at Nicotinic Cholinergic Receptors

Actions at Muscarinic Cholinergic Receptors

Biogenic Amines Derived from amino acids Catecholamines – derived from tyrosine - Dopamine - Norepinephrine (noradrenaline) - Epinephrine (adrenaline) Norepineprine and epinephrine bind adrenergic receptors - Alpha and beta adrenergic receptors - Slow responses at all adrenergic receptors Adrenergic receptors are G-protein-coupled Generally linked to second messengers

Dopamine Category: biogenic amine Postsynaptic effect: Excitatory or inhibitory Fig. 6.11

Dopamine Receptors Large diversity of metabotropic dopamine receptors (at least 6). Bound by many antipsychotic drugs Kandel, 2000

Norepinephrine Category: biogenic amine Formed from dopamine also in PNS sympathetic NS

Norepinephrine Receptors Effect depends on receptor bound α-receptors α1- vs. α2-receptors (see next slide) ß-receptors Silverthorn 2004

Receptors can be Located Presynaptically too – This will determine their effect Presynaptic GABAB receptor actions Isaacson, J Neuophysiolgy, 1998

Epinephrine Category: biogenic amine synthesized from norepinephrine Effect depends on receptor bound α-receptors ß-receptors

Histamine Category: biogenic amine Postsynaptic effect: Excitatory Fig. 6-12

Histamine effects Receptors are all G-protein coupled In brain, affects arousal and attention In periphery affects inflamation, vasodilation. Why do some cold medicines make you sleepy? (good exam question).

Serotonin (5-HT) Category: Biogenic amines Postsynaptic effect: Excitatory

Serotonin effects Involved in sleep/wakefulness cycle Most receptors are metabotropic, but one group are ionotropic. Why does turkey make you sleepy? SSRI and depression

Amino Acid Neurotransmitters Amino acid neurotransmitters at excitatory Synapses: glutamate Amino acid neurotransmitters at inhibitory Synapses: GABA (gamma-amino butyric acid)

Glutamate Category: small-molecule Glutaminergic neurons Postsynaptic effect: depends Very important in CNS Synthesized from glutamine from glia Fig. 6.6

Glutamate Receptors Ionotropic Metabotropic NMDA AMPA kainate late EPSP Glycine & Mg2+ dependent AMPA early EPSP kainate Metabotropic Kandel 2000

GABA (γ-aminobutyric acid) Category: small-molecule GABAergic neurons Postsynaptic effect: Inhibitory Made from glucose Fig. 6.8

GABA Receptors GABAA – Ionotropic GABAB – Metabotropic gates Cl- channel GABAB – Metabotropic gates K+ channel Fig. 6.9

Neuropeptides Short chains of amino acids E.G., endogenous opiates - endorphins – found in the brain, morphine-like - Vasopressin – Anjtidiuretic hormone (ADH) – found in the posterior pituitary

Autonomic Nervous System (ANS) Both branches of the ANS innervate most effector organs Primary function – regulate organs to maintain homeostasis Parasympathetic and sympathetic activities tend to oppose each other - Parasympathetic Nervous system – rest - Sympathetic nervous system – fight or flight response

Autonomic Pathways

Neurotransmitters and their Receptors in the ANS