NEU 490 Quiz 5 Postsynaptic Receptors & NTs Flashcards
Ionotropic: acts BLANK and receptors change shape when they are bound by a BLANK and this change in shape creates a BLANK that allows BLANK to flow through - NT bind on BLANK side - direct BLANK
Can lead to postsynaptic potentials - both same ??
Ligand gated ?
Proteins that bind the neurotransmitter (on extracellular side) causes BLANK change and contain an BLANK through which ions can pass either BLANK or BLANK (eg, Na+, Ca++, K+, Cl-)
Examples: Nicotinic ACh receptors, NMDA and AMPA glutamate receptors, GABAa receptors, 5-HT3 receptors (serotonin), P2X receptors (ATP)
Inotropic: Nicotinic ACh receptor channel activation - which 4 happens?
Ionotropic: acts quickly and receptors change shape when they are bound by a ligand and this change in shape creates a channel that allows ions to flow through - NT bind on extracellular side - direct depolarization
Can lead to postsynaptic potentials - both same signed(EPSP depo) and opposite signed(IPSP hypo) to lead to threshold
Ligand gated transmembrane proteins: proteins that span the cell membrane
Proteins that bind the neurotransmitter (on extracellular side) causes conformational change and contain an ionophore through which ions can pass either cations or anions (eg, Na+, Ca++, K+, Cl-)
Examples: Nicotinic ACh receptors, NMDA and AMPA glutamate receptors, GABAa receptors, 5-HT3 receptors (serotonin), P2X receptors (ATP)
Inotropic: Nicotinic ACh receptor channel activation - membrane depo - AP excitation - muscle contraction
Metabotropic → once BLANK binds activate g-protein and leads to the cascades → takes a BLANK longer depending on the number of steps required to produce a response, metabotropic receptors do not have BLANK and receptors activates a G-protein that in turn activates a BLANK, that in turn will activate something else. Consequence can be receptors activation may or may not result in the BLANK of ion or BLANK channels somewhere else on the membrane. G-protein on BLANK side - called G-protein bc can be activated by GTP
Can lead to postsynaptic potentials - both same ??
Ligand gated ??
Proteins that are the “front end” of intracellular enzymatic cascades. Classic types are the seven ?
Examples: muscarinic ACh receptors excite or inhibit (G-prot; PLC), Beta-adrenergic receptors (G-prot; cyclases), GABAb receptors, 5-HT1(serotonin) receptors, D1-5 receptors(dopamine), MGluRs (glutamate), peptides like CGRP and substance P
Metabotropic: Muschrinsic ACh receptor activation - release of alpha/beta GTP from ?? tell me steps to decrease HR
Metabotropic → once NT binds activate g-protein and leads to the cascades → takes a little longer depending on the number of steps required to produce a response, metabotropic receptors do not have channels and receptors activates a G-protein that in turn activates a secondary messenger, that in turn will activate something else. Consequence can be receptors activation may or may not result in the opening of ion or closing channels somewhere else on the membrane. G-protein on intracellular side - called G-protein bc can be activated by GTP
Can lead to postsynaptic potentials - both same signed(EPSP depo) and opposite signed(IPSP hypo) to lead to threshold
Ligand gated transmembrane proteins: proteins that span the cell membrane
Proteins that are the “front end” of intracellular enzymatic cascades. Classic types are the seven transmembrane spanning region proteins
Examples: muscarinic ACh receptors excite or inhibit (G-prot; PLC), Beta-adrenergic receptors (G-prot; cyclases), GABAb receptors, 5-HT1(serotonin) receptors, D1-5 receptors(dopamine), MGluRs (glutamate), peptides like CGRP and substance P
Metabotropic: Muschrinsic ACh receptor activation - release of alpha/beta GTP from heteromeric G protein - activation of inward rectifier K channel by Beta - membrane hypo of K leave cell - decrease heart rate
NT responses at receptors:
– One neurotransmitter can bind to both ?
– These can elicit the same effects, or can elicit opposite effects
– based on subtype receptor binds to has opposite effects
—- Acetylcholine activity at Nicotinic ACh receptor - ???
— Acetylcholine activity at Muscarinic ACh receptor - ??
Cellular Receptors:
– G-protein coupled receptor - ?
– Channel linked receptor - ?
– Enzyme linked receptor - ??
– Nuclear receptors - in nucleus and require ?
NT responses at receptors:
– One neurotransmitter can bind to both ionotropic and metabotropic receptors
– These can elicit the same effects, or can elicit opposite effects
– based on subtype receptor binds to has opposite effects
—- Acetylcholine activity at Nicotinic ACh receptor - ionotropic and excitatory allows NA in for depo
— Acetylcholine activity at Muscarinic ACh receptor - inhibitory metabotropic for K leaving for hypo
Cellular Receptors:
– G-protein coupled receptor - metabotropic receptors
– Channel linked receptor - ionotropic receptors
– Enzyme linked receptor - kinase which requires phosphorylation - intracellular signaling
– Nuclear receptors - in nucleus and require ligand to cross membrane to bind to neucels not common in neuronal signaling but other cell types - typically hormones
Most ligand receptors are membrane proteins:
– Receptors act as BLANK sites for neurotransmitters and hormones. Exogenous substances bind to existing recognition sites
– Most ligand receptors are transmembrane proteins
– Neurotransmitters and related drugs which interact with receptors to stimulate the natural response are frequently termed BLANK
– In contrast, BLANK interact with receptors to prevent the response
– Drugs can be either agonists or antagonists
Ligand-receptor interactions Agonists:
– Act at BLANK concentrations (micromolar or less) - psychological relevant
– Structure is greatly influenced by small changes in chemistry
– Can be antagonized selectively; for example if I was study dopamine signaling then there are global dopamine antagonist so better to use specific subtype like D2 receptors
– Activity of the antagonists is also greatly influenced by changes in chemical structure.
The consequence of a drug-receptor interaction is a physiological change which can be measured and its magnitude plotted against drug concentration to produce a graded dose-response relationship (whole animal is mg/kg only) - if study cell tissue uses concentration(mg/ml) response
– EPSP amplitude response or withdrawal threshold response so then can examine shift in dose/concentration compared to the response curve with different perturbations????
Most ligand receptors are membrane proteins:
– Receptors act as recognition sites for neurotransmitters and hormones. Exogenous substances bind to existing recognition sites
– Most ligand receptors are transmembrane proteins
– Neurotransmitters and related drugs which interact with receptors to stimulate the natural response are frequently termed agonists
– In contrast, antagonists interact with receptors to prevent the response
– Drugs can be either agonists or antagonists
Ligand-receptor interactions Agonists:
– Act at low concentrations (micromolar or less) - psychological relevant
– Structure is greatly influenced by small changes in chemistry
– Can be antagonized selectively; for example if I was study dopamine signaling then there are global dopamine antagonist so better to use specific subtype like D2 receptors
– Activity of the antagonists is also greatly influenced by changes in chemical structure.
The consequence of a drug-receptor interaction is a physiological change which can be measured and its magnitude plotted against drug concentration to produce a graded dose-response relationship (whole animal is mg/kg only) - if study cell tissue uses concentration(mg/ml) response
– EPSP amplitude response or withdrawal threshold response so then can examine shift in dose/concentration compared to the response curve with different perturbations(an alteration of the function of a biological system, induced by external or internal mechanisms)
In-Class Question
What is the antagonist used to rescue someone from an opioid overdose?
Research affinities of this drug compared to something like heroin, and then compare that to fentanyl. How does this drug’s affinity make it useful for reversing overdoses?
What is the antagonist used to rescue someone from an opioid overdose?
Answer: Narcan naloxone MU opioid receptor
Research affinities of this drug compared to something like heroin, and then compare that to fentanyl. How does this drug’s affinity make it useful for reversing overdoses?
Answer: Higher affinity for MU opioid receptor so kicks off whatever opioids are bound to the receptor a precipitated withdrawal and requires higher dose to know off fentanyl
Ionotropic Receptors
Membrane-spanning protein complexes that direct the coupling of the what to the what??
Two functional domains:
1. Extracellular site that binds neurotransmitters; ??????
2. Membrane - spanning domain that ????
Rapid -onset and rapidly reversible ??
Different receptors have different channel permeability - ???
Major classes of ionotropic receptors:
1. A diversity of subunits come together to form ionotropic neurotransmitter receptors.
2. Cysteine Loop Receptors Extracellular Side: ?
3. Ionotropic Glutamate Receptors: ?
4. Purinergic (ATP): ?
Ion Permeability of Ionotropic Receptors - based on amino acids that line the pore - Negative charged amino acids in pore for cation to enter:
1. Excitatory ionotropic receptors
– Example: ?
– ? is the principle ion, for some receptors they allow calcium through as well
2. Inhibitory ionotropic receptors
– Example: ??? ; allow Cl in but HC03 leave
– ?? is principle ion
– Many times chloride gradient maintained by K/Cl cotransporter - pumps chloride out of the cell and potassium into cell
Membrane-spanning protein complexes that direct the coupling of the neurotransmitter receptor to the ion channel.
Two functional domains:
1. Extracellular site that binds neurotransmitters; NT bind leads to a conformational change that creates an ion pore so the amount of the time that NT is bound affects the postsynaptic repose
2. Membrane -spanning domain that forms an ion channel
Rapid -onset and rapidly reversible synaptic transmission
Different receptors have different channel permeability - excite or inhibit
Major classes of ionotropic receptors:
1. A diversity of subunits come together to form ionotropic neurotransmitter receptors.
2. Cysteine Loop Receptors Extracellular Side: nACh(nicotinic acetylcholine), GABAa, Glycine, 5HT3(serotonin)
3. Ionotropic Glutamate Receptors: AMPA, Kainate, NMDA
4. Purinergic (ATP): P2X, P2Z
Ion Permeability of Ionotropic Receptors - based on amino acids that line the pore - Negative charged amino acids in pore for cation to enter:
1. Excitatory ionotropic receptors
– Example: AMPA receptors
– Sodium is the principle ion, for some receptors they allow calcium through as well
2. Inhibitory ionotropic receptors
– Example: GABAa receptors; allow Cl in but HC03 leave
– Chloride is principle ion
– Many times chloride gradient maintained by K/Cl cotransporter - pumps chloride out of the cell and potassium into cell
G-protein Coupled Receptors (eg, Metabotropic Receptors)
Heterotrimeric G-proteins versus Monomeric Gproteins - Termination of signaling for both GTP hydrolysis to GDP
Two main types of metabotropic receptors, both of which are GTPbinding proteins:
- Heterotrimeric G-proteins are composed of ?
– There are a dizzying number of G-protein permutations
– G-proteins alpha, beta, gamma attach to subunit ? - Monomeric G-proteins relay signals from ?
– Ras, Rho, and Rac
– Adaptor protein GEF
– GTPase activating proteins GAP
– Ras regulate cells ?
General principle of the heterotrimeric GPCR signaling system
1. Activate Enzymes (α-GTP)
2. Inhibit Enzymes (α-GTP)
For both inhibit or activate: weather they do either determined if they ???????
3. Directly modulate Ion Channels (βγ)
G-protein Coupled Receptors (eg, Metabotropic Receptors)
Heterotrimeric G-proteins versus Monomeric Gproteins - Termination of signaling for both GTP hydrolysis to GDP
Two main types of metabotropic receptors, both of which are GTPbinding proteins:
- Heterotrimeric G-proteins are composed of alpha, beta, and gamma subunits.
– There are a dizzying number of G-protein permutations
– G-proteins alpha, beta, gamma attach to subunit alpha exchanges GDP for GTP leads to dissociation of betta and gamma subunits which affect the effector protein or nearby ion channels - Monomeric G-proteins relay signals from activated cell surface receptors to intracellular targets
– Ras, Rho, and Rac
– Adaptor protein GEF
– GTPase activating proteins GAP
– Ras regulate cells differentiation and proliferation
General principle of the heterotrimeric GPCR signaling system
1. Activate Enzymes (α-GTP)
2. Inhibit Enzymes (α-GTP)
For both inhibit or activate: weather they do either determined if they are excitatory or inhibitory receptors and if alpha activate these is dissociation of beta and gamma subunits they stay together and alpha goes to nearby enzymes to increase or decrease GDP
3. Directly modulate Ion Channels (βγ)
Different G-protein subtypes → the reason why postsynaptic response of metabotropic receptors are so diverse is alpha subunits are GS, Gi, or Gq
Gs – stimulatory:
1. Activates ???
2. cAMP acts as a second messenger, activating protein kinase A (PKA) - ????
3. This goes on to phosphorylate several proteins within the cell - ????
Gi – inhibitory:
1. Inhibits ???
2. Subsequent decrease in intracellular levels of ??
Gq – its arbitrary - typically excite but can be inhibitory:
1. Activates phospholipase??????
2. IP3 induces release of ???
3. Depo of Ca as 2nd message and endoplasmic reticulum goes to elicits ???
4. Phospholipid PIP2 is within the cellular membrane and splits to either ?????
Different G-protein subtypes → the reason why postsynaptic response of metabotropic receptors are so diverse is alpha subunits are GS, Gi, or Gq
Gs – stimulatory:
1. Activates adenylyl cyclase, which converts ATP into cAMP
2. cAMP acts as a second messenger, activating protein kinase A (PKA) - increase concentration of cAMP and kinases like to phosphorylate things so AC to ATP to CAMP - proteins require phosphorylation like a switch to be turned on or off which is a tool for activation
3. This goes on to phosphorylate several proteins within the cell - long lasting postsynaptic changes
Gi – inhibitory:
1. Inhibits adenylyl cyclase
2. Subsequent decrease in intracellular levels of cAMP and reduction in the activity of PKA
Gq – its arbitrary - typically excite but can be inhibitory:
1. Activates phospholipase C (PLC), which in turn cleaves the phospholipid PIP2 (phosphatidylinositol) into two products, IP3 and DAG
2. IP3 induces release of calcium from intracellular stores
3. Depo of Ca as 2nd message and endoplasmic reticulum goes to elicits release of Ca stores from IPS
4. Phospholipid PIP2 is within the cellular membrane and splits to either IP3(is what goes to ER and elicit release of Ca stores leads to depo) or DAG
Effector pathways associated with Heterotrimeric G-protein–coupled receptors:
NT Norepinephrine, Receptor B-adrenergic, G-protein Gs stimulatory, Effector protein Adenylyl cyclase, Second messenger cAMP, Later effectors Protein kinase A, Target action: ???
NT Glutamate, Receptor mGluR, G-protein Gq, Effector protein Phospholipase C PLC, Second messenger either DAG OR IP3, Later effectors either Protein kinase C OR Ca release, Target action: ???????
NT Dopamine, Receptor D2, G-protein Gi, Effector protein Adenylyl cyclase, Second messenger cAMP, Later effectors Protein kinase A, Target action: ???????
Effector pathways associated with Heterotrimeric G-protein–coupled receptors:
NT Norepinephrine, Receptor B-adrenergic, G-protein Gs stimulatory, Effector protein Adenylyl cyclase, Second messenger cAMP, Later effectors Protein kinase A, Target action: Increase protein phosphorylation
NT Glutamate, Receptor mGluR, G-protein Gq, Effector protein Phospholipase C PLC, Second messenger either DAG OR IP3, Later effectors either Protein kinase C OR Ca release, Target action: Increase protein phosphorylation and activate Ca binding proteins
NT Dopamine, Receptor D2, G-protein Gi, Effector protein Adenylyl cyclase, Second messenger cAMP, Later effectors Protein kinase A, Target action: Decrease protein phosphorylation
Targets and Removal Mechanisms:
Second Messenger Cyclic AMP with Gs or Gi; Sources Adenylyl cyclase acts on ATP; Intracellular targets Protein kinase A cyclic nucleotide gated channels; Removal mechanisms cAMP ??? – Can open what ??
Second Messenger Cyclic AMP with Gs or Gi; Sources Guanylyl cyclase acts on GTP; Intracellular targets Protein kinase G cyclic nucleotide gated channels; Removal mechanisms cGMP ???
Second Messenger IP3 with Gg; Sources Phospholipase C acts on PIP2; Intracellular targets IP3 receptors on endoplasmic reticulum; Removal mechanisms ??
Second Messenger Diacylglycerol DAG with Gg; Sources Phospholipase C acts on PIP2; Intracellular targets Protein kinase C; Removal mechanisms ??
PIP2 either IP3 OR DAG
Neuronal second messengers – Gs and Gi:
1. Gs open ?
2. Gi closes ?
Neuronal second messengers- Gq – IP2 located in the BLANK and is split between ??? Caused by??
15 PKC isozymes: conventional, novel, and atypical
1. Conventional PKCs protein kinase C (PKCα, βI, βII and γ) require both? ??
2. Novel PKCs can be activated by ???
3. Atypical PKCs do not require????
Targets and Removal Mechanisms:
Second Messenger Cyclic AMP with Gs or Gi; Sources Adenylyl cyclase acts on ATP; Intracellular targets Protein kinase A cyclic nucleotide gated channels; Removal mechanisms cAMP Phosphodiesterases (PDEs are enzymes that break down cyclic nucleotides) – cAMP is a cyclic nucleotide and cAMP can open nearby CNG-gated channels
Second Messenger Cyclic AMP with Gs or Gi; Sources Guanylyl cyclase acts on GTP; Intracellular targets Protein kinase G cyclic nucleotide gated channels; Removal mechanisms cGMP Phosphodiesterases (PDEs are enzymes that break down cyclic nucleotides)
Second Messenger IP3 with Gg; Sources Phospholipase C acts on PIP2; Intracellular targets IP3 receptors on endoplasmic reticulum; Removal mechanisms Phosphates
Second Messenger Diacylglycerol DAG with Gg; Sources Phospholipase C acts on PIP2; Intracellular targets Protein kinase C; Removal mechanisms Various enzymes
PIP2 either IP3 OR DAG
Neuronal second messengers – Gs and Gi:
1. Gs open energy cyclic nucleotide gated channels
2. Gi closes nearby cyclic nucleotide gated channels
Neuronal second messengers- Gq – IP2 located in the membrane and is split between IP3 and DAG and split is caused by PKC:
15 PKC isozymes: conventional, novel, and atypical
1. Conventional PKCs protein kinase C (PKCα, βI, βII and γ) require both calcium and diacylglycerol (DAG) for their activation.
2. Novel PKCs can be activated by DAG alone.
3. Atypical PKCs do not require DAG nor Ca2+ for their activation
In Class Question
There are many diseases that are elicited by dysfunction of g-protein coupled receptors. Research: what are two examples of diseases that are caused by either mutation or dysfunction of GPCRs?
Retinitis pigmentosa a mutation of GPCR of photoreceptors - Rhodopsin - GPCR for rods - lose night vision and peripheral
Schizophrenia dopamine receptors GPCR hyper activity
Hyper or hypothyroidism - thyroid receptors
Neuronal second messengers – Late Effectors
Second Messenger Ca 2+ Increases in ?????????? and close the ???????
Sources Plasma Membrane: VG Ca channels(sometimes CNG Ca channel or IP3 gated Ca channels) and various ligand gated channels + ER: IP3 receptors and Ryanodine receptors (release ???
Intracellular targets Calmodulin, protein kinases, protein phosphatase, ion channels, synaptotagmin, many other Ca binding proteins that can lead to long lasting changes and can activate protein and enzymes important for????
Removal mechanisms Plasma Membrane: ????????
Ca2+ toxic if not maintained at low levels within cell but with long lasting high inside is bad
Ca pump: remove Ca to BLANK and pump in BLANK via ion exchange
- Ca Pump on ER uses ??? To??
- Ca binding buffer proteins help buffer the ??
Targets of second messengers: PKC, PKA, CAMKII, non-receptor tyrosine kinase PPI, PP2A; PP2B (calcineurin) – activated by cAMP and Ca
Second Messenger Ca 2+ Increases in Gs or Gi open and Gq close the Ca channels
Sources Plasma Membrane: VG Ca channels(sometimes CNG Ca channel or IP3 gated Ca channels) and various ligand gated channels + ER: IP3 receptors and Ryanodine receptors (release intracellular stores)
Intracellular targets Calmodulin, protein kinases, protein phosphatase, ion channels, synaptotagmin, many other Ca binding proteins that can lead to long lasting changes and can activate protein and enzymes important for gene transcription - long lasting change
Removal mechanisms Plasma Membrane: Na/Ca exchanger and Ca pump + ER: Ca pump + Mitochondria
Ca2+ toxic if not maintained at low levels within cell but with long lasting high inside is bad
Ca pump: remove Ca to ECF and pump in H+ via ion exchange
- Ca Pump on ER uses ATP to pump Ca back into ER
- Ca binding buffer proteins help buffer the high intracellular Ca concentrations
Targets of second messengers: PKC, PKA, CAMKII, non-receptor tyrosine kinase PPI, PP2A; PP2B (calcineurin) – activated by cAMP and Ca
Acetylcholine is the only low-molecular-weight aminergic transmitter substance that is not an amino acid or derived directly from one.
Nervous tissue cannot BLANK choline, which is derived from the diet and delivered to neurons through the bloodstream.
Foods with highest amounts of choline:
Meat, eggs, poultry, fish, and dairy products.
Potatoes and cruciferous vegetables such as brussels sprouts, broccoli, and cauliflower.
Some types of beans, nuts, seeds, and whole grains.
Acetylcholine is synthesized in nerve terminals from the precursors ???????? (acetyl CoA, which is synthesized from glucose) and choline, in a reaction catalyzed by choline acetyltransferase - in our ??
Vesicular acetylcholine transporter pumps ACH into vesicle and 2 protons out - ATP is ????
Acetylcholine is the only low-molecular-weight aminergic transmitter substance that is not an amino acid or derived directly from one.
Nervous tissue cannot synthesize choline, which is derived from the diet and delivered to neurons through the bloodstream.
Foods with highest amounts of choline:
Meat, eggs, poultry, fish, and dairy products.
Potatoes and cruciferous vegetables such as brussels sprouts, broccoli, and cauliflower.
Some types of beans, nuts, seeds, and whole grains.
Acetylcholine is synthesized in nerve terminals from the precursors acetyl coenzyme A this we have in our neurons (acetyl CoA, which is synthesized from glucose) and choline, in a reaction catalyzed by choline acetyltransferase - in our neurons derived from glucose (have glucose source doesn’t matter)
Vesicular acetylcholine transporter pumps ACH into vesicle and 2 protons out - ATP is an exchanger to get protons to then help pump ACH in to fill vesicle in axon terminal
Which neurons express Acetylcholine?
Acetylcholine was the first substance identified as a neurotransmitter.
Acetylcholine is released at all vertebrate ??????
In the ANS, it is the transmitter released by all ????????
In sympathetic only pre ganglion and in parasympathetic it is pre and post ganglion very close to effector organ – ???
Motor neurons in the ventral horn of spinal cord that are highly ??????
Which neurons express Acetylcholine?
Acetylcholine was the first substance identified as a neurotransmitter.
Acetylcholine is released at all vertebrate NMJ by spinal motor neurons.
In the ANS, it is the transmitter released by all preganglionic neurons which cells body in CNS and have by parasympathetic and sympathetic(right near spinal cord which is chain of ganglia cell bodies) pre which all release Ach or on medulla. Postganglionic neurons release norepinephrine, not Ach.
In sympathetic only pre ganglion and in parasympathetic it is pre and post ganglion very close to effector organ – ACh tend to be muscarinic receptors can be inhibit or excite
Motor neurons in the ventral horn of spinal cord that are highly myelinated and release Ach on muscles that is always excitatory and depo in muscle
Acetylcholine Receptors
Nicotinic ACh receptors (nAChRs):
1. Ligand-gated ionotropic receptors located on ???
2. nAChRs are pentameric structures that are made up of combinations of individual subunits. Either ???
3. Exclusively excitatory, elicits ??
4. Gate allows who into cell ??
Muscarinic ACh receptors:
1. Ligand-gated G-protein-coupled receptors that regulate ??
2. Can be excitatory or inhibitory, eliciting either ??
3. Stimulatory M????
4. Inhibitory M??
Acetylcholine Receptor:
1. CNS ?
2. Autonomic ?
3. Neuromuscular ??
Nicotinic ACh receptors (nAChRs):
1. Ligand-gated ionotropic receptors located on muscle cells and in the CNS
2. nAChRs are pentameric structures that are made up of combinations of individual subunits. Either homomeric 5 alpha or heterometric 3 alpha and 2 beta but both also Ca and Na into emmerbane and is only excite
3. Exclusively excitatory, elicits depolarization of the postsynaptic cell
4. Gate allows Ca and Na into cell
Muscarinic ACh receptors:
1. Ligand-gated G-protein-coupled receptors that regulate numerous fundamental functions of the CNS and PNS.
2. Can be excitatory or inhibitory, eliciting either depolarization or hyperpolarization of the postsynaptic cell.
3. Stimulatory M1, M3, M5 - Gq (converters with PLC IP2 into DAG and IP3 which causes increase of Ca intracellular)
4. Inhibitory M2, M4 - Gi/Go (inhibits conversion of cyclic AMP bc inhibits adenylate cyclase)
Acetylcholine Receptor:
1. CNS (muscarinic and nicotinic)
2. Autonomic (muscarinic and nicotinic)
3. Neuromuscular (nicotinic) - exclusive excitatory in muscles to stimulate contractions
