Introductory Neurobiology Week 4 Day 2 Notes
Introductory Neurobiology Week 4 Day 2 Notes Biol 3640
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This 4 page Class Notes was uploaded by lucy allen on Sunday January 31, 2016. The Class Notes belongs to Biol 3640 at University of Denver taught by Dr. John C Kinnamon in Fall 2016. Since its upload, it has received 14 views. For similar materials see Introductory Neurobiology in Biology at University of Denver.
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Date Created: 01/31/16
Transient Receptor Potential Channels -name comes from a mutation in the photoreceptors of the fruit fly, shining light in the eye of a mutant fly causes a brief receptor potential -inactivates quickly Second Messenger Systems -involved in a number of TRP channels -GPCR is typically composed of seven transmembrane alpha helices, and a receptor on the extracellular side, and a g-protein on the intracellular side -g protein typically contains a large alpha subunit and two smaller beta and gamma subunits -stimulated by a neurotransmitter, activates the G protein -swaps GTP for GDP, activated alpha subunit moves through the membrane until it finds an enzyme which when activated will produce a second messenger -can act directly on an ion channel, can phosphorylate a protein, can cause a cascade of reactions eventually leading to regulation of transcription in the nucleus -phospholipase C pathway -stimulation of GPCR, alpha subunit takes PIP2 and cleaves it, removing it from leaflet of membrane and separates it into DAG and IP3 -DAG can act on an enzyme -IP3can act on the smooth ER, binding to an IP 3eceptor allowing calcium movement into the cytoplasm from the smooth ER -beta-gamma subunit might do something also -olfactory -odorant molecule binds to a G protein -G-olf alpha subunit stimulates adenylate cyclase, which converts ATP to cAMP, which opens cyclic nucleotide gated channel, a cation channel -sodium and calcium come in -calcium activates a calcium activated channel Calcium Metabolism -can act directly on TRP channel and open it up, or can enhance the activity of the TRP channel What Are TRP Channels? -identified in all species to date, vertebrates and invertebrates, with the exception of bacteria (so far) -there are six families of TRP channels -TRPV1 sensitive to heat (chili peppers) -TRPV2 sensitive to heat -TRPC channels involved in gender identification in rodents -TRPM channels include TRPM5 (bitter, sweet, umami taste) TRPM8 (cool, menthol taste) -ANKTM -TRPA1: wasabi or ginger -common theme to TRP channels is receptors -six transmembrane subunits -C terminus and N terminus -six segments in each domain which are transmembrane and there is a selectivity loop/filter hanging down -open channel allows small monovalent cations to pass through and depolarize the cell Functions of TRP Channels -yeast: hypertonicity (saltiness) -nematodes: noxious chemicals -male mice: pheromones -humans: sweet, bitter, umami, temperature, pain -mechanosensation -hearing -only speculation of involvement of hearing in humans, evidence is currently lacking Theories of TRP Channel Activation -by reducing the amount of PIP 2his enhance the function of the TRP channel -DAG may turn on TRP channels -IP3 opens up the smooth ER and releases calcium and calcium itself make activate TRP channels -ligands (capsaicin, Icilin etc.) -direct activation: changes in temperature (TRPV1-TRPV3, TRPM8; mechanical activation) TRPV Family/Vanilloid Receptor Family -VR1=TRPV1; VRL-1=TRPV2 -TRPV1 -receptor and an ion channel -at body temperature in your mouth you have a lot of unmyelinated sea fibers with loads of TRPV1 channels -at body temperature the ion channel is closed -if you have something very acidic that can open the ion channel -if you drink something hot, (excess of 42 C) will open the TRPV1 channel -if you have chili pepper at body temperature the ion channel will open -fat soluble capsaicin diffuses through phospholipid bilayer and binds intracellularly to the ion channel causing it to open -branches of trigeminal nerve (cranial nerve #5) -mandibular nerve (splits to inferior alveolar nerve and lingual nerve) -maxillary nerve -ophthalmic nerve (nose), ethmoid nerve (nose) -ophthalmic nerve (eye), ciliary nerves (cornea) Scoville Scale -relative burn of some common peppers -bell pepper (0 Scoville units) -Jalapeño (2,000-5,000 units) -Serrano (5,000-15,000 units) -Thai (50,000-100,000 units) -Habañero (100,000-300,000 units) -TRPV2 -sensitive to heat but not chili peppers -responds to hotter temperatures than TRPV1 -something that would actually burn you will open this channel, from 50 Celsius up -TRPV3 -thermosensitive: responds to slightly below body temperature (>31 C) -TRPV4 -thermosensitive: responds to >25 C o -responds to osmotic pressure -ex: in blood plasma, mice who are TRPV4 double knock- outs cannot control the osmolarity of their blood plasma, eat too much salt TRPM Family -temperature -chemical senses -TRPM5 -triggered by bitter, sweet, and umami flavor -signaling pathway is the same for all three -beta gamma subunit, when activated, goes to phospholipase C beta 2, an enzyme in the membrane, stimulated to break up PIP to 2 DAG and IP 3 -downstream the calcium goes to the TRPM5 channel in the membrane allowing entering of sodium, depolarizes the voltage gated sodium channel and the taste cell is depolarized -TRPM8 o -stimulated by cold temperatures, <26 C -stimulated by methanol or Icilin -menthol -neurons in mouth -ice cube -neurons in skin -slide 35 shows the cells that are activated in the presence of certain stimuli -difference between 2nd/3rd and 4th square show that different neurons express TRPV1 vs. TRPM8 TRPP Channels -polycystic kidney disease (PKD1L3) -respond to acidic conditions (low pH) -TRPA1 -noxious cold (doubtful) -horseradish -mustard oil -delta9-tetradhydrocannabinol -cinnamaldehyde -ginger -humans are one of the few species that seek out painful stimuli -also thought to be involved in mechanosensitivity -olfaction -osmosensation -TRPA1 and TRPV1 can be in the same neuron -it has been speculated that they can even interact with each other -TRPA1 and Zinc Dust -everyday things we ingest through the air make us cough or sneeze -TRPC2 -pheromone detection in mice -male mice that lack TRPC2 do not display stereotypical male- male aggression responses and mate indiscriminately with male or female mice -lack of pheromone evoked neuronal activity in the vomeronasal organ (VNO) -TRPC3 -small specialized set of ganglion cells that are photoreceptors, involved in sending information to the hypothalamus to regulate circadian rhythm -TRPC5 in Amygdala -double knockout mice exhibit diminished innate fear levels in response to innate aversive stimuli -Garlic
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