How neurons communicate: Transduction of electricalchemical signal

The neuromuscular junction

Depolarization at the presynaptic terminal causes transmitter release

Na+ influx or K+ eflux not necessary for transmitter release

I/O curve of presynaptic depolarization vs. transmitter release

Ca2+ influx in the pre-synaptic terminal triggers transmitter release

Steep, non-linear relationship

Time course of Ca2+ influx and transmitter release

The calcium hypothesis

Ca2+ channels far more abundant at the presynaptic terminal. In active zone, Ca2+ is 10 times more abundant than elsewhere in the presynaptic terminal. Ca2+ serves a dual purpose: Carrier of depolarizing charge during the action potential Special signal carrying information about action potential to intracellular machinery for transmitter release

A calcium sensor (low-affinity, requires high concentrations of Ca2+).

Presynaptic Ca2+ channels concentrated opposite postsynaptic ACh receptors

red: Ca2+ channels green: ACh receptors

Transmitter released in quanta

miniature end-plate potential

What accounts for the quantized endplate potential?

Fixed postsynaptic response Postsynaptic response to to opening of single ACh channel opening of single Ach channel is smaller than mini (0.3 mV vs. 0.5 mV), which implies ~2000 channels must be open
Presynaptic transmitter release is quantized

1. Is transmitter release quantized during actual synaptic transmission? 2. Does Ca2+ affect: a) size of each quantum b) number of quanta

3. What determines number of quanta released by an AP?

Transmitter released in quanta

Transmitter stored in SVs, released by exocytosis

Review
1. What causes transmitter release? Depolarization. 2. What is necessary for transmitter release? Ca2+ channels 3. Experiments to prove the role of calcium in transmission. 4. What is not necessary for transmitter release? Na+, K+ current. 5. How does calcium play a role? Calcium hypothesis 6. What is quantal hypothesis? Transmitter release is quantized. 7. Ca2+ affects number, not size of quantum, Exp. evidence. 8. Support of quantal hypothesis: a) Physiological b) Structural 9. Structural evidence: SVs, exocytosis, all SV contents excreted. 10.Exocytosis? Endocytosis? 11. Modelling transmitter release? Binomial distribution. Poisson approximation.