CBNS 120 Synaptic Transmission I: Electrical & Direct (Ionotropic) Chemical Transmission

The word "synapse" was coined by:

Sir Charles Sherrington (1897): "a special connection of one nerve cell with another."

Electrical synapses are:

Low-resistance current pathways between cells formed by gap junction channels (connexons).

Gap junction channels are composed of:

Connexin (vertebrates, 20 types) and pannexin (vertebrates, 3 types) or innexin (invertebrates, >25 types).

Gap junctions allow passage of molecules up to:

~1000 Da (1 kD) (e.g., ATP, cAMP, IP3).

Functions of electrical synapses include:

Allowing small molecule passage (development), reducing synaptic delay, synchronizing neuronal activity.

The coupling coefficient (k12) of an electrical synapse is:

k12 = V2/V1 = R2/(R2+Rc). As Rc (gap junction resistance) increases, synaptic strength decreases.

- k12 is for a voltage generated in V1

what is the relationship between R₂, R_c, and k₁₂?

• if R2 is large compared to RC, k12 will approach unity.

• but if R2 is small compared to RC, k12 will be small.

Rectifying electrical synapses pass current:

Better in one direction than the other (e.g., crayfish lateral giant to giant motor axon; Furshpan & Potter, 1959).

• depolarizing current anterogradely

Directionality of electrical synapses:

it can vary, some are bidirectional, some are unidirectional, or rectifying

Rectification in Drosophila giant fiber synapses is due to:

Heterotypic gap junction channels (different innexins) that are asymmetrically gated by voltage which underlies rectification (Phelan et al., 2008).

The amphibian ciliary ganglion is an example of:

A combined electrical and chemical synapse.

what is the ciliary ganglion?

parasympathetic ganglion in posterior orbit of eye

• controls ciliary muscle for lens thickening & circular iris muscle for pupil constriction.

Otto Loewi (1921) proved:

Chemical transmission of nerve impulses (Vagusstoff = acetylcholine). Nobel Prize 1936 with Henry Dale.

Importance of acetylcholine

the first neurotransmitter to be identified

The four classes of synaptic vesicles by morphology are:

Light core spherical (excitatory),

light core ovoidal (inhibitory),

small dense core (catecholamines/indolamines),

large dense core (neuropeptides).

At chemical synapses, transmitter-gated ion channels are:

Where the neurotransmitter receptor and ion channel are parts of the same protein (ionotropic receptors).

Direct (ionotropic) receptors include:

Nicotinic AChR, 5-HT3, GABAA/GABAC, glycine, and ionotropic glutamate receptors (NMDA, AMPA, kainate).

The six general steps in chemical synaptic transmission are:

1) AP depolarizes terminal

2) depolarization activates Ca2+ conductance

3) vesicles move to active zones

4) vesicles fuse and release transmitter

5) transmitter binds postsynaptic receptors

6) ion channels open/close, producing PSP (postsynaptic potential).

Whether a neurotransmitter is excitatory or inhibitory depends on:

The type of receptors in the postsynaptic membrane (not the transmitter itself).

At the vertebrate neuromuscular junction:

ACh is always excitatory (opens non-selective cation channels, depolarization to 0 mV, EPP).

Acetylcholinesterase (AChE) breaks down ACh into:

Acetate + choline (rate-limiting step in repolarization).

α-bungarotoxin and curare:

Block nicotinic ACh receptors.

Organophosphates (e.g., sarin, VX) inhibit:

Acetylcholinesterase (causing prolonged ACh action).

The reversal potential for synaptic currents is:

The membrane potential at which the postsynaptic current changes from inward to outward (measured by voltage clamp).

Inhibitory postsynaptic potentials (IPSPs) at spinal motor neurons are mediated by:

Increased Cl- conductance (shunting inhibition; Coombs, Eccles & Fatt, 1955).

Presynaptic inhibition (e.g., crayfish claw opener) occurs when:

GABA released onto excitatory presynaptic terminal activates Cl- conductance, reducing excitatory transmitter release.