e.g., ACh receptorsNicotinic, MuscarinicGlutamate receptorsAMPA, NMDA, kainate, and mGluRsMajor Categories of Receptors:Ionotropic receptors (transmitter-gated ion channels)Fast synaptic transmission;Sensitive detectors of chemicals and voltage;Directly regulate flow of ionic currents;Differentiate between similar ions;Amino Acid-Gated ChannelsGlutamate-Gated ChannelsAMPA, NMDA, kainateAmino Acid-Gated ChannelsGABA-Gated and Glycine-Gated ChannelsBoth mediate fast inhibitory synaptic transmissionGlycine receptors (spinal cord), GABA (brain)Metabotropic receptors (G-protein-coupled receptors)Multiple steps mediating signaling:Binding of the neurotransmitter to the receptor proteinActivation of G-proteins (homomeric and trimeric forms)Exchange of GDP to GTP on alpha subunitActivation of effector systemsThe Basic Structure of G-Protein-Coupled Receptors (GPCR)Single polypeptide with seven membrane-spanning regionsActivation of G-proteins (exchange of GDP to GTP; dissociation of α and βγ subunits) can lead to several intracellular effects:1. Direct binding to ion channels (e.g., free βγ subunits bind and open K+ channels – action of Ach in heart!)2. Binding of α subunit to effector proteins, and production of “second-messengers” (e.g., binding to adenylate cyclase increases cAMP concentrations)3. Activation (or inhibition) of second-messengers induce further changes mediating modulation of metabolic activity, channel functions, gene expression!Actions of metabotropic receptors are usually:much slower than ionotropic receptors (10s of msec to minutes!);of longer durations;extensively amplified, comparedto ionotropic receptor actionsA Few More Categories of Receptors:3. Enzyme-linked receptors (e.g., tropomyosin receptorkinase – trk; Toll-like receptors - TLRs): they activate a variety of intracellular signaling pathways.Intracellular receptors (often hormone receptors that respond to lipophilic chemicals that can cross lipid membranes relatively freely): often translocate to the nuclei and work as transcription factors.RECEPTOR LOCATIONPost-synaptic receptorsPre-synaptic receptorsHeteroreceptors: respond to NT other than the ones contained in its synaptic vesicles.Autoreceptors: respond to NT that are released from it’s own synaptic vesicles (usually inhibitory.NRSC 2100 1st Edition Lecture 10Neurotransmitter receptors:I. Receptors are transmitter-gated proteinsII. Together with neurotransmitters, receptors work in a “ Lock and Key ”arrangement.III. There have been 100 ’ s of receptors isolated that respond to a variety of chemical neurotransmitters IV. Several receptor proteins can bind the “same” neurotransmitter(ex., ACh binds both “nicotinic” and “muscarinic” receptors).V. Studying Receptor Subtypes • e.g., ACh receptors – Nicotinic, Muscarinic• Glutamate receptors– AMPA, NMDA, kainate, and mGluRsMajor Categories of Receptors:Ionotropic receptors (transmitter-gated ion channels)– Fast synaptic transmission;– Sensitive detectors of chemicals and voltage;– Directly regulate flow of ionic currents;– Differentiate between similar ions;• Amino Acid-Gated Channels– Glutamate-Gated Channels• AMPA, NMDA, kainateThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.Amino Acid-Gated Channels– GABA-Gated and Glycine-Gated Channels • Both mediate fast inhibitory synaptic transmission • Glycine receptors (spinal cord), GABA (brain)Metabotropic receptors (G-protein-coupled receptors)• Multiple steps mediating signaling:– Binding of the neurotransmitter to the receptor protein– Activation of G-proteins (homomeric and trimeric forms)– Exchange of GDP to GTP on alpha subunit– Activation of effector systems • The Basic Structure of G-Protein-Coupled Receptors (GPCR)– Single polypeptide with seven membrane-spanning regionsActivation of G-proteins (exchange of GDP to GTP; dissociation of and α subunits) can lead to several intracellular effects:βγ1. Direct binding to ion channels (e.g., free subunits bind and open βγK+ channels – action of Ach in heart!)2. Binding of subunit to effector proteins, and production of α “second-messengers” (e.g., binding to adenylate cyclase increases cAMP concentrations)3. Activation (or inhibition) of second-messengers induce further changes mediating modulation of metabolic activity, channel functions, gene expression!Actions of metabotropic receptors are usually:• much slower than ionotropic receptors (10s of msec to minutes!);• of longer durations;• extensively amplified, compared to ionotropic receptor actionsA Few More Categories of Receptors:3. Enzyme-linked receptors (e.g., tropomyosin receptorkinase – trk; Toll-like receptors - TLRs): they activate a variety of intracellular signaling pathways.Intracellular receptors (often hormone receptors that respond to lipophilic chemicals that can cross lipid membranes relatively freely): often translocate to the nuclei and work as transcription factors.RECEPTOR LOCATION• Post-synaptic receptors• Pre-synaptic receptors• Heteroreceptors: respond to NT other than the ones contained in its synaptic vesicles.• Autoreceptors: respond to NT that are released from it’s own synaptic vesicles (usually