Ion channels and neuronal excitability Flashcards
How is electricity produced?
The source of electricity lies in the atom.
Electrical currents are generated through movement of electrons.
Atom can be neutral, positively charged or negatively charged.
Electrical currents in neurons occur due to movement of positively and negatively charged ions inside and outside of the cell membrane which results in electrical potential differences in the neuronal membrane that is measured in millivolts (mV).
How do ions move across the neuronal membrane?
Ions (Na+, K+, Ca2+, Cl-) are hydrophilic and are unable to penetrate the hydrophobic lipid bilayer of the membrane.
Therefore, neurons expressed a plethora of ion channels that facilitate diffusion of ions across the cell membrane.
Direction of ion movement into and out of the cell depends on:
Electrical gradient: negative ions move towards positive charges and vice versa.
Chemical gradient: ions move from higher concentration to lower concentration to reach equilibrium (ions tend to move through chemical more than electrical).
Why is there more K+ inside and Na+ outside of the membrane?
In order for neurons to function, they have to maintain an electrical potential difference across the cell membrane.
Sodium/potassium pump uses energy to transport 3 Na+ outside, 2 K+ inside keeping high conc of Na+ outside and high conc of K+ inside.
Needs energy to fight against gradient - given by ATP.
The inside of the cell then becomes relatively more negatively charged compared to the outside.
What causes an action potential gradient?
Neurons communicate through synapses where neurotransmitters are released from pre-synaptic axon terminals and bind to receptors expressed on the membrane of post-synaptic neurons.
This results in production of small electrical current called post-synaptic potentials in the post-synaptic neuron.
These include:
Inhibitory post-synaptic potentials (IPSP).
Excitatory post-synaptic potentials (EPSP).
Balance of EPSPs / IPSPs arriving at dendrites determines if a cell becomes more positive (depolarise) or negative (hyperpolarise).
Enough depolarisation results in generation of an action potential at the axon hillock, sends on an electrical signal to the synapse.
What are the two action potential refractory periods?
Absolute refractory period:
Due to inactivation of sodium channels – it is absolutely not possible to generate an action potential.
Relative refractory period:
Due to potassium channels being open – resulting in outward K+ leak, makes the cell membrane less excitable, but sodium channels are reactivated and an action potential can be generated with a greater stimulus.
How do leak channels work?
Channels open and close randomly.
No stimulus required.
How do ligand-gated channels work?
Activated in response to binding of a chemical ligand to a specific protein subunit, activating the ion channel.
E.g. GABAa and NMDA receptors.
How do mechanically-gated channels work?
Mechanical stimulus required.
E.g. sensors for stretch.
How do voltage-gated channels work?
Activated in response to depolarisation of membrane (change in voltage across the membrane).
Contains a voltage sensor.
What is the resting membrane potential determined by?
Concentration of Na+ and K+ across the cell membrane.
Due to chemical gradient, K+ tends to diffuse outside through leaky K+ channels whereas Na+ diffuses inside.
However Na+ channels are less leaky than K+ channels.
Less Na+ will diffuse in than K+ out; leads to slight negative charge inside the membrane.
K+ ions continue to move outside of the cell until membrane potential of -70 mV is reached.
What is the role of excitatory post-synaptic potentials (EPSPs)?
Depolarisation: opening of Na+ (or Ca2+) channels leading to positive ions entering cell.
This increases membrane potential (i.e. becomes less negative).
Generally, triggered by ligand-gated ion channel (e.g. glutamate receptor) then propagates on the membrane.
What is the role of inhibitory post-synaptic potentials (IPSPs)?
Hyperpolarisation: opening of K+ or Cl- channels; positive ions (K+) leave or negative ions (Cl-) enter cell.
This decreases membrane potential (becomes more negative).
Can be triggered by ligand-gated ion channel (e.g. GABA receptor, glycine receptor).
What are the phases of an action potential?
Resting potential: difference in voltage across the neuronal membrane - 70mV.
A stimulus reaches the neurons and produces EPSPs which depolarise the cell to -55mV (threshold).
At -55 mV a sudden rush of Na+ ions into the cell occurs due to low concentration of Na+ inside the cell which raises the voltage to +30/+40 mV (depolarisation).
At +30/40 mV Na+ channels inactivate and K+ become activated which leads to K+ leaving the cell due to high concentration of K+ inside the cell; this lowers the voltage back down (repolarisation).
