Disease as a synaptic modulator

Chemical Electrical

Synapse structure discontinuity continuity

Directionality Uni (?) Bi (?)

Speed moderate (1-1.5 ms) FAST (0.1 ms)

(escape networks)

Threshold high none

PSP shape transmitter removal same as pre

Pathologies:

Epilepsy: coupling strength may be greater

in hyperexcitable brain regions

Seizures- worse in children where

neurons are more extensively coupled.

Charot-Marie-Tooth disease; mutation in Cx32,

Affects gap junctions in Schwann cells.

Cx26, Cx 31- sensorineural deafness- defects in

K+ and glutamate buffering.

Protozoan infections:

Chargas’ disease

HIV opportunistic infections

Cardiomyopathies,

astrocyte coupling affected

Modulation of electrical synapses: Dopamine reduces electrical coupling in the retina!

and dye transfer between horizontal cells!

Control! DA!

Sites for modulatory action!

Remember V= IR!

Snail voltage-clamp experiments

Compare tau with crayfish

synaptic potential decay

Snail two electrode recordings

1) Determine Rin and tau

2) Voltage Clamp

ICm Iion

ICm

Current Clamp

Poor V- Clamp

Good V- Clamp

ICm

Iion

Total Iion,

No blockers

Itail

- 50 to 0 mV

-80 mV

-50 mV

Tail currents

Determining reversal potential for K from tail current

Voltage clamp of squid giant axon