L14 GABA

define neurotransmitters

chemical messengers released from one neuron and acting at a close site on another to elicit an effect determined by the specific nature of the receptor

what is acetylcholine for

voluntary movement of the muscles

what is glutamate used for

major excitations - roles in memory and learning

what is dopamine used for

• motivation

• pleasure associated with addiction and love

what is serotonin used for

emotions, wakefulness and temperature regulation

what is GABA

the major inhibitory neurotransmitter

what is ATP used for

neuronal/glial communication, role in pain regulation

what are neurotransmitter agonists

ligands causing a postsynaptic effect

why are neurotransmitter agonists referred to as ‘endogenous agonists’

made by the body

what are neurotransmitter antagonists

ligands which block the action of the agonist

what was the nobel prize in 1936 given to Otto Loewi and Henry Dale for

the existence of chemical neurotransmitters (vagusstoff)

what was the nobel prize in 1970 given to Bernard Katz for

the nature of synaptic transmission

what was the nobel prize in 1991 given to Bert Sakmann and Erwin Neher for

analysis of single ion channel behaviour

the smallest postsynaptic release arises from…

the release of neurotransmitter from one vesicle

what is the contents of one vesical of neurotransmitter referred to as

a quanta

how are single vesicles released

spontaneously

what is the postsynaptic response name of single vesicles

a mini

what dictates the decay of neurotransmitter currents

persistant ACh application produces persistant current

• not indefinitely as AChs desensitize

how does [ACh] vary with time

Q₁₀= 2.8

• diffusion dominated processes have a Q₁₀= ~1

what is the relation of [ACh] and time with current

voltage dependence of decay (faster at more negative holding potentials)

where are nicotinic (ACh) acetylcholine receptors found

at the neuromuscular junction (muscle cells) and between pre and postsynaptic cells in the ANS (also electric rays)

what are ACh receptors permeable to

Na+, K+ and Ca2+

what is the Erev of ACh receptors

~-5mV

how many subunits does the adult form of ACh receptors have

5

what are the 5 subunits of ACh receptors adult form

• 2 alpha

• 1 beta

• 1 delta

• 1 theta

what does the adult alpha subunit bind (in ACh receptors)

ACh

• 2ACh bind per receptor

give an example of ACh receptor antagonists

• alpha-bungarotoxin (snake venom)

• curare compounds (plants)

describe myasthenia gravis

• autoimmune disease

• body produces autoantibodies against nicotinic ACh receptors

• EPP can’t generate muscle stimulation

• 2nd subset of M.g

• autoantibodies against muscle specific kinase (MuSK)

what are GABA_A, GABA_C and glycine receptors

ionotropic

what is GABA_B receptor

metabotropic

what are GABA_A, GABA_C and glycine receptors permeable to

Cl- and HCO3-

what is the Erev ratio of GABA_A, GABA_C and glycine receptors

~4:1 E_rev to E_Cl

since E_Cl is close to E_m and below the action potential threshold, GABA_A, GABA_C and glycine receptors tend to be

inhibitory

what is the structure of GABA_A, GABA_C and glycine receptors

pentameric

describe 5HT₃ receptors

• pentamers

• similar transmembrane loops

• Na+, K+, Ca2+ permeability

• (other 5HT-Rs are metabotropic)

what does GABA-R subunit composition dictate

• receptor properties

• cell surface distribution

• dynamic regulation

give examples of receptor properties

• sensitivity

• conductance

• kinetics of opening and closing

describe GABA delta subunits

sensitive with low desensitisation

what do GABA delta subunits mediate

tonic GABAergic currents

what does point mutation remove sensitivity to

pentobarbital

describe the modulation of synaptic receptors of GABA alpha

• benzodiazepines (eg diazepam)

• mediate secretion

• bind at interface of alpha/gamma 2 subunits

describe the modulation of extrasynaptic barbituate receptors of GABA alpha

increase the affinity of GABA

describe the modulation of extrasynaptic neurosteroidal receptors of GABA alpha

both positive and negative allosteric modulation

describe the modulation of extrasynaptic alcoholic receptors of GABA alpha

enhances GABA action

what do barbiturates do

‘lock’ GABA receptors in the open state

what do benzodiazepines do

ease opening of receptors

give an example of a P1 metabotropic agonist

adenosine

give an example of a P2Y metabotropic agonist

nucleotides, ATP, UTP, ADP, UDP

give an example of a P2X ionotropic agonist

ATP

what permeability do P2X ionotropic agonists have

Na+, K+ and Ca2+ permeability

what expression do P2X ionotropic agonists have

widespread glia and neuronal

where is ATP released for P2X ionotropic agonists

synaptic vesicles

what types of purinergic receptors (ATP) are there

• P1

• P2

• P2X

what is the P2X ionotropic agonist an important means of

neuronal to glial, and glia-to-glia, communication