lecture 7 - Action potentials Flashcards
The action potential:
- the fundamental unit of information in the nervous system
- “an action potential is a short-lasting event in which the electrical membrane potential of a cell rapidly rises and falls
action potentials Occurs in several types of cell (‘excitable’ cells), including:
Neurons
Muscle cell
Cardiac cells
Endocrine cells (such as pancreatic beta cells)
When we say “short-lasting”…
An action potential lasts 1-2 ms (depending on species, cell type, temperature etc)
types
Many cells have an electrical potential across the membrane.
This is most evident in ‘excitable’ cells. In these cells, the resting membrane potential is negative relative to extracellular space (usually somewhere between -50 and -90 mV)
The phases of an action potential
Membrane potential is dependent on …
leak K+ channels
Voltage-gated Na+ channel structure: an overview
A large single alpha subunit ion-conducting pore
4 domains (I-IV), each containing 6 transmembrane segments
Voltage-sensors on the 4th transmembrane segment
One or more beta subunits regulation of gating, kinetics and expression
Voltage-gated Na+ channel structure: an overview
Voltage-gated Na+ channel-mediated depolarisation triggers a ‘chain reaction’
During an action potential Na+ channels open, further depolarising the membrane potential, opening more Na+ channels
Voltage-gated Na+ channels rapidly inactivate after activation
Voltage-gated Na+ channels rapidly inactivate after activation
Voltage-gated K+ channels are also activated by depolarisation, but more slowly
Na+ channel inactivate.More slowly activated voltage-gated K+ channels are activated.
Ionic mechanisms of the action potential: a summary
Saltatory condution
Myelination
Myelin sheath insulates the axon from external –ve charge i.e. decreases membrane capacitance and increases resistance across the membrane ->
Faster transmission
However, the myelinated axon still has some capacity to store charge
So the signal (carried by +vely charged cations) degrades; cannot be amplified by additional Na+ channels
The solution: Nodes of Ranvier act as signal boosters
High density of voltage-gated Na+ and K+ channels at Nodes of Ranvier
When a propagating action potential reaches the Node a ‘new’ action potential is initiated.
Known as saltatory conduction (from the Latin saltare, to leap)
Action potential diversity
a )Purkinje neuron in the cerebellum (Equilibrium and fine movement). AP in this region are very brief only last 180 microsecond.
In contrast CA1 neurons of the hippocampus (b) tend to they tend to last more, around 800 microseconds and are followed by a slowly decaying after depolarization
Two examples from the hippocampus
- CA1 pyramidal neuron
- Oriens-Lacunosum moleculare interneuron
CA1 pyramidal neuron
Glutamatergic ‘principal’ cell
Afferents:
CA3 pyramidal cells
Entorhinal cortex
Various hippocampal GABAergic neurons
Efferents
Subiculum
Entorhinal cortex
Prefrontal cortex
Various GABAergic interneurons
Oriens-Lacunosum moleculare interneuron
GABAergic interneuron
Afferents:
Hippocampal pyramidal cells
Medial septum
Other interneurons
Efferents
Distal dendrites of CA1 pyramidal neurons
Other interneurons
Action potential waveforms
Pyramidal neurons – most likely to secrete Glu – Most abundant excitatory NT in the CNS
OLM interneuron – GABAergic – Inhibitory
Differences in action potential waveform: threshold
CA1 threshold is more hyperpolarized (lower) than O-LM interneuron
Proprieties of the ion channels influence thresholds
Voltage-gated sodium channel α-subunit subtypes
Measuring activation properties of Na+ currents
Implications in AP threshold
NaV1.1 Channels, found in OLM interneurons, have a more depolarised V1/2 (less negative) compared to CA1 pyramidal neurons.
This means that half of the Na+ channels are opened at a more hyperpolarised level of the membrane potential.
Differences in activation properties of Na channels isoforms contribute to threshold differences
Functional consequences of different AP thresholds
Larger after-hyperpolarising potentials (AHP) in OLM cells
Different firing patterns between cell types
OLM cells have larger AHPs than pyramidal cells
OLM cells fire faster than pyramidal cells
Is there a link?
To answer this, we need to understand some more properties of sodium channels…
Resting state the gate is closed
Depolarizing stimulus polarity of the membrane changes gates are opened
Inactivation gate closes the pore from the inside inactivated channel (can’t be activated)
Voltage-gated channel activation states are dependant on… voltage
Voltage-gated channel activation states are dependant on… voltage
Voltage-gated channel activation states are dependant on… voltage
Voltage-gated channel activation states are dependant on… voltage
Recovery from inactivation depends on time…
it takes time for channels to move from inactivated to closed state
Channels will open again proportionally to the amount of time passed since the first depolarizing stimulus
voltage
Recovery from inactivation depends on the voltage steps.
The more hyperpolarised the membrane between pulses, the larger the second pulse
Back to our example action potentials
summary
Neuronal action potentials are generated by activation of voltage-gated Na+ channels and terminated by inactivation of these channels and activation of voltage-gated K+ channels
Whilst action potentials have generalised form, there is some diversity in AP waveforms in different cells driven by diversity in expression of different voltage-gated channels
Differences in action potential waveform can contribute to differences in action potential firing patterns
