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This 3 page Class Notes was uploaded by Maymie Gaylord on Monday September 21, 2015. The Class Notes belongs to BIOL 6102 at Georgia State University taught by Staff in Fall. Since its upload, it has received 8 views. For similar materials see /class/209920/biol-6102-georgia-state-university in Biology at Georgia State University.
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Date Created: 09/21/15
Biol 6102 Neurobiology Sept 9 2008 Intracellular Signal Transduction Chapter 6 Styles of Neuronal communication 0 Synaptic Pointtopoint o paracrine local hormone volume transmission endocrine hormonal Types of Signaling molecules Cellimpermeant neurotransmitters o Cellpermeant steroid and thyroid hormones gases Cellassociated cell adhesion molecules Four Types of Receptors 1 Ionotropic Receptors Ligandgated ion channels 2 Metabotropic or Gprotein Coupled Receptors GPCR 3 Enzymelinked Receptors Receptor Tryrosine Kinases growth factor receptors 4 Intracellular Receptors Soluble guanylyl cyclase steroid nuclear receptors Ionotropic Receptors o Nicotinic Acetylcholine Receptors nAChR c Exogenous agonist nicotine Antagonists oc bungarotoxin curare Five subunits two on subunits amp 3 others 3 y 5 s The on subunits have the ACh binding sites Neuronal and Muscle nAChRs differ sensitivity to antagonists subunit composition Ca2 permeability o Glutamate Receptors AMPAKainate Receptors Ionotropic Poreblocker MK801 requires glycine as a coagonist Permeable to Ca2 in addition to Na K Voltagedependent conductance o caused by Mg2 block of the pore Slower kinetics of opening and closing Properties are important for synaptic plasticity and excitotoxicity o GABA receptors GABAA and GABAC receptors are ionotropic Exogenous agonist muscimol Antagonist bicucculine Channel blocker picrotoxin Exogenous agonists AMPA Kainate Antagonist CNQX Permeable to both Na K Erev OmV Rapid kinetics of opening and closing NMDA Receptors Ionotropic Exogenous Agonist NMDA NmethyIDaspartate Antagonist APV I I I I Allosteric modifiers benzodiazepines such as Valium and barbiturates CI39 channels Erev 50mv p1 GProtein Coupled Receptors GPCR Metabotropic receptors ansmembrane spanning domains 0 Heterotrimeric GTPbinding Proteins G proteins mediate most ofthe actions of G proteincoupled receptors 0c 3 y subunits When the receptor is activated on subunit exchanges GDP for GTP oc subunit with GTP dissociates from 3 In some cases By can directly activate a protein such as an ion channel muscarinic receptor the shortcut pathway oc subunit can activate effector proteins Can be positively or negatively coupled to effector Gs and Gi oc subunit has GTPase activity and stimulated by GTPaseActivating Proteins GAP hydrolyzes GTP to GDP allowing up and yto reassociate Primary Effector Proteins ead to production of Second Messengers Diffusible molecules that convey signal inside the cell cAMP IP3 DAG and Ca2 are examples 0 Adenylyl Cyclase produces cAMP from ATP cAMP is broken down by Phosphodiesterases PDE cAMP can activate Protein Kinase A PKA cAMP binds to regulatory subunits allowing catalytic subunits to dissociate PKA can phosphorylate proteins cAMP can also directly open cyclicnucleotidegated ion channels Leads to amplification of signal 0 Phospholipase C produces lnositol trisphoshate IP3 and Diacylglycerol DAG from Phosphatidylinositol bisphosphate a membrane lipid P3 acts at receptors to release Ca2 from intracellular stores DAG and Ca2 activate Protein Kinase C PKC PKG translocates to the membrane when activated 0 Ca2 is a common intracellular messenger Elevated in Cytoplasm due to Membrane voltagegated channels Membrane ligandgated channels P3 receptors on the endoplasmic reticulum Mitochondrial release binds to Calmodulin leads to activation of Ca2Calmodulindependent protein kinase type II CaMKII can directly gate ion channels Ca activated K channels Ryanodine receptors Ca2 induced Ca2 release from intracellular tores Ca2 is rapidly removed from the cytoplasm Calcium pump NaJ39ICa2 exchanger Ca2 binding proteins Kinases and Phosphatases Protein phosphorylation is a reversible process Kinases and Phosphatases act in dynamic equilibrium 0 PKA PKG and CaMKH are SerThr kinases 0 Phosphorylation of ion channels and synaptic release proteins p2 Functions of Intracellular signaling omosynaptic Plasticity One neuron alters its own properties as a function of its own activity Sometimes homeostatic in nature synaptic facilitation synaptic depression posttetanic potentiation Long term potentiation o Heterosynaptic Plasticity Neuromodulation One neuron alters the properties of another neuron Alter ion channel activation change excitability Alter receptor sensitivity Alter synaptic release p3
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