NTs 3 Flashcards
major inhibitory NT is? charged? other inhibitory NT?
GABA. neutral. other inhibitory NT = glycine, also neutral
GABA dysfunction associated with? drugs?
epilepsy, Huntington’s disease, tardive dyskinesia, alcoholism, sleep disorders. anticonvulsant, anti-anxiety and sedative drugs enhance GABA function
neutral amino acid NTs: main mechanism?
increase Cl- permeability. IPSPs.
chloride movement at RMP?
RMP = - 60 mV which is less than ECl. so Cl comes in, and you get an EPSP. influx down concentration gradient more important than electrical gradient
Cl- movement at -110 mV?
Em = -110 mV which is greater than ECl. Cl leaves cell = reversed IPSP, since electrical gradient larger
reversal potential for Cl-
-80 mV. when Em = ECl so chemical gradient and electrical gradient is balanced, no net movement of Cl-. stimulation of channels won’t alter membrane potential
current voltage relationship of IPSP: what it looks like at different membrane potentials
strongly depolarized = large IPSP. RMP = normal IPSP. -80 mV aka reversal/equilibrium potential: flat line. strongly hyperpolarized: reversed IPSP now Cl is leaving the cell
where is GABA made and broken down
GABA made in neurons. then transported into astrocytes where it is broken down
GABA synthesis: how?
glutamate, glutamaic acid decarboxylase GAD converts it into GABA
marker for GABA neurons
GAD: glutamic acid decarboxylase which converts glutamate to GABA
GABA breakdown: where and how
in astrocytes, with GABA-T (gaba transmiaminase. at the same time it breaks GABA down, it transfers amino group to a-ketoglutarate to make glutamate
breakdown of GABA by ____ provides?
by GABA-T: provides NH2 for synthesis of glutamate
after GABA is made: transported into? how?
transported into vesicles with a transporter that depends on electrical potential across vesicular membrane
released GABA: then what happens?
taken up and recycled via Na/Cl dependent transporter. also taken up into glia and metabolised by GABA-T to succinic semialdehyde while a-ketoglutarate is made into glutamate
glutamaic acid decarboxylase not present where? present where? so implication?
not found in glia, only in neurons. so released glutamate is taken back into neurons where it is converted into GABA.
GABA-T involved in?
synthesis and metabolism of GABA
GABA-A receptors: structures
similar to nAChR: give subunits each with different gene products. each subunit has 4 TM domains.
AAA vs. IAA structure
acidic/excitatory AA receptors: 4 subunits with 3 TM domains. inhibitory AA receptors: 5 subunits X 4 TM domains
GABA-A receptors: site of action for what drugs
anxiolytic benzodiazephines, sedatie and hypnotic drugs like barbiturates and ethanol
bicuculline
selective GABA-A receptor antagonist, convulsant
GABAZINE
GABA-A antagonist, aka SR 95531
picrotoxin
blocks Cl channel of GABA A receptor, is a convulsant
synaptic vs. extrasynpatic GABA-A receptors: subunits
synaptic GABA - A receptor most abundant isoform is a1b2y2. important is having a1. extrasyanptic found further away, a4b3d
extrasynaptic GABA-A receptors: sensitizing? location? what type of inhibition
slowly desensitize, located away from cleft, may be tonically activated by ambient GABA levels = tonic not phasic synpatic inhibition.
