neurotrans 123

neurotransmitters3.md

@@ -15,6 +15,13 @@ As we’ve shown in our examples earlier the nAChR receptor is a non-selective c
 
 *nAChR permeable to Na+, K+, and Ca2+*
 
+In physiological solution, calcium flux estimated to be 2% of total current through nAchR. For comparison calcium flux is estimated to be 7% of the current in the voltage gated L-type calcium ion channel. But with high density clustering of many nAchRs at muscle end plate synapses, total calcium flux through these channels could influence the local environment significantly https://doi.org/10.1523/JNEUROSCI.10-10-03413.1990 
+
+This Ca^2+^ permeability depends on subunit composition of the nAchR pentamer. mammalian α9α10 receptors receptors show higher calcium ion selectivity (important function in cochlear hair cells) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4245820/
+
+
+
+
 from [#Picciotto:2000]:
 >some subtypes of nAChR in the brain (those containing the b2 subunit) are located diffusely throughout the membrane of the neuron, with no obvious concentration at the synaptic junction (Hill et al. 1993).
 
@@ -205,6 +212,8 @@ Note:
 * alternative splicing of each of the 4 subunit genes can result in a number of more isoforms
 * GluR1 and GluR2 especially important in synaptic plasticity by being upregulated
 
+* Non-selective cation channel like nAChr, but tetramer and less calcium permeability. mRNA editing of a intramembrane domain of the GluR2 subunit switches a glutamine to an arginine. This post translational modification results in AMPA receptors that have resistance to calcium permeability. Though AMPA-R usually contain one or more GluR2 subunits, ones that are missing GluR2 subunits do have more calcium permeability and may be important in developing neurons and early forms of synaptic plasticity in some neurons https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3092818/
+
 
 ---
 
@@ -376,11 +385,19 @@ Note:
 * 5-HT3 is a ligand-gated non-selective cation channel, thus it is excitatory
     * Same basic structure as nACh receptor
 * All others are metabotropic– likely that perturbations in these receptors are involved in many neural disorders
+  * excitatory: 5-HT2,4,6,7
+  * inhibitory: 5-HT1,5
+
 
 Note:
 
 most receptors are metabotropic
 
+* 7 members of family
+* 5HT1, 5HT5 are Gi: inhibitory (decr cAMP)
+* 5HT2,4,6,7 are Gs or Gq: excitatory (incr cAMP or incr IP3/DAG)
+* 5HT3 is non selective ionotropic cation channel (excitatory)
+
 ---
 
 ## Catecholamine receptors
@@ -392,6 +409,8 @@ most receptors are metabotropic
 
 Note:
 
+* more examples of catecholamine metabotropic receptors in action later in course (e.g. dopamine D1, D1 types in basal ganglia function)
+
 
 ---