Lecture 2 (Sept 9) - Neurotransmission & Drug Discovery PDF

Lecture 2 (Sept 9): Need to Know from Text and Notes Know the roles of the different glia cells Know the different types of receptors on the presynaptic and postsynaptic membranes - know the difference between autoreceptors and heteroreceptors - know how ionotropic vs. metabotrop...

Lecture 2 (Sept 9): Need to Know from Text and Notes Know the roles of the different glia cells Know the different types of receptors on the presynaptic and postsynaptic membranes - know the difference between autoreceptors and heteroreceptors - know how ionotropic vs. metabotropic receptor activation leads to ion channel opening - know metabotropic receptors activate a 2nd messenger system inside the neurons to affect ion channels, you do not need to know each step in this 2nd messenger system Know how the different processes of neurotransmission are ended, and why this is important. Know how EPSP’s and IPSP’s are generated and their contribution to postsynaptic integration of information and impact on action potential generation - know the difference between voltage dependent and ligand gated ion channels Know where drugs can work to modulate these different components of neuronal transmission (all of the above points). This will also be expanded on in coming lectures. 1  Lecture 2 (Sept 9): Need to Know from Text and Notes Know the different families of ion channels for voltage dependent and ionotropic/ligand gated channels (for example Na v, Cav, P2X, TRP, nAChR...) - know the activators for the different ionotropic/ligand gated channels - know which ions flow across the different channels (voltage dependent and ionotropic/ligand gated), and what is the end result: excitation or inhibition of the neuron) - you do not need to know the subtypes in each voltage dependent family (for example Nav1.1, Nav.1.2, Cav2, Cav3...), but know that their activation is linked a specific voltage range (Nav is activated by low (negative) voltage, Cav has high and low voltage channels, and Kv has mainly high voltage (positive) channels) Know how NaV channels were initially defined Know the different subtypes of ionotropic glutamate receptors and how they are activated Know that TRPV1 is activated by heat and capsaicin; TRPA1 is activated by wasabi, mustard oil, cinnamaldehyde, gingerol, and environmental toxins; and TRPM8 is activated by menthol and cool/cold. - you do not need to know the other activators for TRP channels or the other TRP channels listed 2  Lecture 2 (September 9): Need to Know from Text and Notes Know each of the neurotransmitters, what categories they belong to (e.g., monoamines), their ligands, the mechanisms for reuptake and degradation (where this takes place), and which receptors are inhibitory (including if they are post-synaptic, or an autoreceptor or heteroreceptor) or excitatory - for the receptors, focus on the “oddball” ones, for example, α2 NA receptors are the inhibitory ones (so the rest like α1 and β1,2 are excitatory) - know the origin brain sites/pathways for Acetylcholine (Ach), Dopamine (DA), Noradrenaline (NA or NE), histamine, and serotonin (5-HT): a strong emphasis on key associations (NA = locus coeruleus, serotonin = raphe, histamine =TMN), and the 3 dopamine pathways - know that glutamate and GABA are found throughout the CNS (and have major excitatory and inhibitory, respectively, roles) - know which group (I, II, III) of metabotropic glutamate receptors are located post-synaptically and which are autoreceptors/heteroreceptors (and if excitatory or inhibitory) - know how lipid and peptide transmitters are released and how they can communicate with other cells. Know examples of each - you do not need to know the different functions/behaviors associated with the neurotransmitters or their pathways (although this will be a requirement when we study the individual diseases) 3  Lecture 2 (September 9): Need to Know from Text and Notes Know and describe the different steps in modern drug discovery - know the differences between the different stages of clinical studies - you do not need to know about the cost or length of studies The text and class notes overlap quite a bit, from the text know content in subsections of chapter 2 (LO 2.3, 2.10-2.16), and chapter 4 (LO 4.10-4.14). - you do not need to know tables 4.2 or 4.6 in the text 4