GABAergic synaptic transmission

where is GABA stored before release

small synaptic vesicles inside nerve terminals (axon tips) of GABAergic neurone

what triggers GABA release

action potential arriving at terminal → depolarisation → opening of voltage-gated Ca2+ channels → Ca2+ influx

what is the role of Ca2+ in neurotransmitter release

Ca²⁺ binds to proteins that mediate fusion of vesicles with the plasma membrane, releasing GABA into the synaptic cleft

what happens when GABA binds to GABA_a receptors in the synaptic cleft

Cl⁻ ions flow into the postsynaptic neurone (and some HCO₃⁻ out), causing hyperpolarisation due to accumulation of these negatively charged ions

what is IPSP (inhibitory postsynaptic neurone)

transient hyperpolarisation (below -70mV) that makes neurone less likely to fire action potential

what happens when multiple IPSPs occur close together in time or space

they summate, causing stronger hyperpolarisation

how do IPSPs interact with EPSPs

IPSPs can cancel or reduce EPSPs, returning the membrane potential toward the resting state (−70 mV) — this is synaptic inhibition

where can GABAergic synapses be found

on dendrites, soma, and axons, including the axonal initial segment (AIS), where they can strongly inhibit action potential generation

what does drug bicuculline do

competitive antagonist of GABAₐ receptors, blocking GABA binding and inhibiting IPSPs

what response remains after bicuculline blocks GABA_a receptors

slow hyperpolarisation mediated by GABAʙ receptors (G-protein-coupled), activating K⁺ channels

how do GABA_b receptors cause hyperpolarisation

by opening voltage-gated K⁺ channels, allowing K⁺ to flow out of the neurone down its electrochemical gradient

what maintains Na+ and K+ concentration gradients in neurones

the Na⁺/K⁺-ATPase pump, which uses ATP to move Na⁺ out and K⁺ in

what are the approximate ion concentrations maintained by Na⁺/K⁺-ATPase

• Na⁺: 150 mM outside / 15 mM inside

• K⁺: 4 mM outside / 110 mM inside

how is the chloride (Cl⁻) gradient maintained

by the K⁺–Cl⁻ cotransporter (KCC2), which pumps Cl⁻ out while bringing K⁺ in

what are the typical Cl- concentration inside and outside neuron

• Outside: ~130 mM

• Inside: ~8–10 mM

why is Cl- gradient essential for GABAergic inhibition

without it, Cl⁻ would not flow into the cell when GABAₐ receptors open, and IPSPs could not be generated

what is the net effect of GABAergic synaptic activity

to inhibit neuronal firing by hyperpolarising the membrane and opposing excitatory inputs