SSRI Synapse: Serotonin Reuptake Inhibition

Drug & Neuron Controls

SSRI dose (SERT blockade) 0%

Presynaptic firing rate 4.0 Hz

Postsynaptic receptor density 30 sites

Live Synaptic State

Synaptic 5-HT

0 nM

Receptor occupancy

SERT reuptake rate

0 mol/s

Legend

Free serotonin (5-HT) Receptor-bound 5-HT Reuptaken (fading) SERT transporter (glows red when blocked)

How it works

At a real serotonergic synapse, an action potential triggers calcium-dependent vesicle fusion, dumping serotonin (5-HT) into the cleft. Two competing processes then set how long it lingers: binding to postsynaptic receptors, and reuptake by the presynaptic serotonin transporter (SERT), which pumps 5-HT back into the terminal for recycling.

SERT reuptake is a saturable, carrier-mediated process described by Michaelis-Menten kinetics. A competitive inhibitor — an SSRI (selective serotonin reuptake inhibitor) — binds the same transporter site as 5-HT itself, raising the apparent K_m without changing V_max:

v = Vmax·[5-HT] / (Km·(1 + [I]/Ki) + [5-HT])

v    = rate of reuptake
Vmax = maximum transporter turnover rate
Km   = transporter affinity for 5-HT (no drug)
[I]  = SSRI concentration,  Ki = drug's inhibition constant

Because Km grows with drug dose, the transporter needs far more serotonin around it to work at the same speed — reuptake slows, synaptic 5-HT accumulates, and postsynaptic receptor occupancy rises. This is the accepted mechanism by which SSRIs (fluoxetine, sertraline, escitalopram, etc.) increase serotonergic signalling; the clinical mood effect follows only after days-to-weeks of downstream receptor adaptation, which this simulator does not model.

SSRI dose slider — scales [I]/Ki, raising the SERT transporters' apparent Km (watch them dim from active gold to blocked red).
Firing rate slider — sets how often the presynaptic terminal fires an action potential and releases a vesicle quantum of 5-HT.
Receptor density slider — number of postsynaptic binding sites available to occupy (structural property of the neuron, not the drug).
Fire action potential — forces one extra release event on demand.

Free 5-HT: 0 Bound: 0 SERT blocked: 0%

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