Action potentials

What is an AP?

→ fundamental unit of info in the NS

‘A short lasting event in which the electrical membrane potential of a cell rapidly rises and falls’

• lasts 1-2ms

• Cells have negative membrane potential compared to extracellular space

Where do action potentials occur

Excitable cells:

• neurons

• Muscle cells

• Cardiac cells

• Endocrine cells

Phases of an action potential simple

1. Action potential threshold is reached, membrane potential depolarised

2. Depolarisation causes an upwards (+ve) spike

3. Membrane rapidly repolarises during the downwards spike

4. Often followed by a temporary additional after hyperpolarisation

Voltage gated Na+ channel

• large alpha subunit→ ion conducting pore

• 4 domains, each with 6 transmembrane proteins

• Voltage sensors on the 4th

• 1+ beta subunits = regulation of gating, kinetics and expression

How do Na+ and K+ channels work?

1. Activation gate opens in response to a depolarisation, AP threshold = -55/60mV

2. Na+ flows into the cell, activates more channels, more flows in = depolarisation

3. Na+ channels rapidly inactivate

4. K+ channels also activated by depolarisation, but much slower

5. K+ ions leaving the cell repolarises the cell, but causes and overshoot = after-hyperpolarisation

6. NaK+ pump resets

How is the resting membrane potential maintained

• leak K+ channels (facilitated diffusion)

• NaK pump (active transport)

Saltatory conduction

→ rapid ‘leaping’ of nerve impulses between gaps in myelin sheath

• electrical resistance in the axon is higher in thinner axons = slower conduction

How does myelination cause saltatory conduction?

Myelin sheath insulates axon from external -ve charge

• higher resistance across membrane

• Lower ability to store charge

Still has some capacity to store charge→ signal degrades

• Nodes of Ranvier = gaps that act as signal boosters

• Lots of Na and K channels in nodes

• When AP reaches node, a new one is initiated

Two examples of action potential diversity

1. Purkinje neuron→ in the cerebellum

• equilibrium and fine movement

• AP are very brief - 180us

2. CA1 neurons → hippocampus

• tense to last longer- 800us

• Slow decay after depolarisation

Two examples from hippocampus

1. CA1 pyramidal neuron→ Glutamatergic

• afferents (towards CNS) = CA3 cells, Entorhinal cortex

• Efferent (away from CNS) = prefrontal cortex, subiculum

2. OLM → GABAergic interneuron

• afferents = hippocampal pyramidal cells, medical septum

• Efferents = distal CA1 dendrites, other interneurons

AP waveforms of hippocampal examples

• CA1 threshold is more hyperpolarisation (lower) than OLM

• Properties of the ion channels influence different threshold

• Peak of depolarisation is higher in CA1

• Larger AHP in OLM neurons

Na+ channel subtypes

• 9 different subtypes

• Properties of each influence thresholds

Measuring activation properties of Na+ current

• the activation of the whole cell is reflected by the no. Of channels open at a certain voltage

• The graph = electrical activity against size of voltage step

• V½ = when half of channels are activated

Different activation properties of CA1/OLM

• NaV1.1 channels in OLM interneurons have a more depolarised V½ (higher) compared to CA1

• Caused by differences in activation properties of Na+ channel isoforms

Firing patterns in the two neurons

• OLM cells have larger AHPs and fire faster than pyramidal cells

3 states of Na+ channels

1. Resting state = gate is closed at -ve membrane potentials similar to resting, but available

2. Depolarising stimulus = polarity of the membrane changes mean the gates open, create in inward current

3. Inactivation gate = closes the pore from the inside = inactivated channel by inactivation gate and are unavailable

Voltage and current graphs between channel phases

What does recovery from initiation depend on?

1. Time→ it takes time for channels to go from inactivated to closed, channels will open proportionally to time since the first stimulus

2. Voltage→ depends on voltage steps , the more hyper-polarised the membrane between pulses, the larger the second pulse