HUBS191

• Ion channels


  Protein embedded channels within the cell membranes that facilitate the movement of ions across the membrane
• Types of ion channels


  • Passive channels
  • Gated channels
• Passive channels


  • Always open, allowing ions to move across the membrane down their electrochemical gradient
  • Example: leak channels, which contribute to the resting membrane potential by allowing a continuous flow of ions
• Types of gated channels


  • Chemically-gated
  • Voltage-gated
  • Mechanically-gated
• Chemically-gated ion channels


  • Respond to the binding of neurotransmitters, leading to changes in membrane permeability
  • When neurotransmitters bind, they open, allowing ions like sodium (Na+) and potassium (K+) to flow in or out of the cell
• Voltage-gated ion channels


  • Open in response to changes in membrane potential
  • Particularly crucial for neurons, they initiate and propagate action potentials
  • When the membrane depolarizes, voltage-gated sodium (Na+) channels open, allowing sodium ions to rush into the cell, leading to depolarization
• Mechanically-gated ion channels


  • Sensitive to mechanical forces, such as stretching or pressure changes
  • Play a role in sensory perception and cellular responses to physical stimuli
• Movement of ions through ion channels

  Alters the membrane potential, which is vital for neuronal communication
• Sodium (Na+) channels


  Allow sodium ions to enter the cell, leading to depolarization
• Potassium (K+) channels


  Allow potassium ions to exit, contributing to repolarization
• Local potentials (graded potentials)


  • Changes in the voltage of the membrane potential at specific areas of the dendrite or cell body membrane
  • Occur when neurotransmitters bind to chemically-gated ion channels, allowing ions such as sodium (Na+) to move in or potassium (K+) to move out, leading to depolarization (EPSP) or hyperpolarization (IPSP) of the membrane
• Local potentials


  Changes in the voltage of the membrane potential at specific areas of the dendrite or cell body membrane
• Local potential generation


  1. Neurotransmitters bind to chemically-gated ion channels

  2. Ions (Na+, K+) move in or out

  3. Depolarization (EPSP) or hyperpolarization (IPSP) of the membrane
• Excitatory Postsynaptic Potentials (EPSPs)


  Form when excitatory neurotransmitters bind to receptors on the postsynaptic membrane, opening chemically-gated sodium channels and causing depolarization, making the neuron more likely to generate an action potential
• Inhibitory Postsynaptic Potentials (IPSPs)


  Form when inhibitory neurotransmitters bind to receptors on the postsynaptic membrane, opening chemically-gated potassium channels and causing hyperpolarization, making the neuron less likely to generate an action potential
• Threshold potential


  Typically around -60mV at the axon hillock, triggers an action potential
• Spatial Summation


  1. Signals from multiple presynaptic neurons meet at the same postsynaptic neuron

  2. Excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs) arrive simultaneously or close together

  3. Their effects summate at the postsynaptic membrane

  4. If the combined effect reaches the threshold for action potential initiation, the postsynaptic neuron may fire
• Temporal Summation


  1. A single presynaptic neuron fires repeatedly in rapid succession

  2. The local potentials generated by each firing overlap in time

  3. If these successive potentials are excitatory and occur close enough together, their effects can summate, potentially reaching the threshold for action potential initiation and leading to neuron firing
• Summation at the axon hillock


  • Inputs from presynaptic neurons are integrated
  • High densities of voltage-gated ion channels, particularly sodium (Na+) channels
  • When the combined effect of inputs surpasses the threshold potential (around -60 mV), voltage-gated Na+ channels open, initiating the depolarization phase of an action potential
• Summation happens at the axon hillock, where inputs from presynaptic neurons are integrated
• Summation is related to threshold potential and generation of an action potential
• Action potential generation


  1. Voltage-gated (VG) Na+ channels open when the membrane depolarizes to around -60mV

  2. Massive influx of Na+ ions, leading to the rapid depolarization phase

  3. At roughly +30mV, VG Na+ channels inactivate, VG K+ channels open, initiating the repolarization phase

  4. As the membrane approaches its resting membrane potential (RMP), VG Na+ channels begin to close

  5. At roughly -90mV, VG K+ channels begin to close slowly, allowing excess K+ to exit and causing hyperpolarization

  6. Once all VG K+ channels close, the membrane returns to its resting potential of around -70mV
• Presynaptic inputs are summed at the axon hillock because it contains a high concentration of voltage-gated ion channels, especially sodium (Na+) channels, necessary for generating action potentials
• The threshold potential, typically around -60 millivolts (mV), triggers the opening of these channels
• When inputs from presynaptic neurons summate to reach or surpass this threshold, voltage-gated Na+ channels open, allowing sodium influx and initiating rapid depolarization
• This depolarization propagates the action potential along the neuron's axon, enabling the transmission of electrical signals to other neurons or target cells
• Summation at the axon hillock determines whether the combined effect of excitatory and inhibitory inputs is sufficient to elicit action potential initiation and activate voltage-gated ion channels
• Action potential propagation in unmyelinated axons


  1. Action potential develops in initial segment

  2. Na+ ions enter and spread away from open voltage-gated channels

  3. Graded depolarization brings membrane in segment two to threshold

  4. Action potential develops in segment two

  5. Initial segment begins repolarization

  6. Na+ ions enter at segment two and spread laterally

  7. Graded depolarization brings membrane in segment three to threshold

  8. Action potential can only move forward, not backward
• Unmyelinated vs Myelinated axons


  • Action potentials propagate along unmyelinated axons relatively slowly (1 to 5 metres per second)
  • Myelination dramatically increases action potential conduction velocity
• Myelin sheath


  Schwann cells (PNS) or oligodendrocytes (CNS) wrap the axon in neighbouring segments
• Nodes (of Ranvier)


  Narrow gaps with no myelin, have high density of voltage-gated Na+ and K+ channels
• Action potential propagation in myelinated axons


  1. Action potential develops at initial segment

  2. Local current produces graded depolarization that brings axolemma at node one to threshold

  3. Action potential develops at node one

  4. Initial segment begins repolarization

  5. Local current produces graded depolarization that brings axolemma at node two to threshold
• Absolute refractory period


  A second action potential cannot be generated, occurs when voltage-gated Na+ channels are already open or become inactive
• Relative refractory period


  A second action potential can be generated only if the stimulus is much larger than normal, occurs when some voltage-gated Na+ channels begin to shift from an inactive to closed state
• Voltage gated Na+ channels cannot open when inactive, they only open from a closed state
• Refractory periods for unidirectional action potentials

  1. Graded depolarization brings membrane to threshold -60 mV

  2. Voltage-gated Na+ channels open, Na+ moves into cell, membrane potential rises to +30 mV

  3. Voltage-gated Na+ channels inactivate, K+ exits cell

  4. Voltage-gated Na+ channels begin to close, can only open with larger stimulus

  5. Voltage-gated K+ channels begin to close slowly, allowing excess K+ exit causing hyperpolarization
• Chemical synapse


  • Presynaptic axon terminal has voltage-gated Ca2+ channels filled with neurotransmitter
  • Synaptic cleft is a space where neurotransmitters diffuse across the postsynaptic membrane, enzymes that inactivate neurotransmitter are present
  • Postsynaptic cell have Chemically-gated ion channels
• Synaptic transmission


  1. Axon terminal depolarizes, voltage-gated Ca2+ channels open, Ca2+ moves into axon terminal

  2. Release of neurotransmitters, Ca2+ causes synaptic vesicles to release neurotransmitters into synaptic cleft, neurotransmitter diffuses across cleft

  3. Formation of local potentials, neurotransmitter binds to chemically-gated ion channels on postsynaptic cell, excitatory neurotransmitters open Na+ channels, inhibitory neurotransmitters open K+ channels
• Termination (end) of synaptic transmission


  Neurotransmitter unbinds from chemically-gated channels, enzymes in synaptic cleft degrade neurotransmitters, portions of degraded neurotransmitter recycled back into axon terminal
• Synaptic transmission example: Cholinergic synapse


  • Action potential triggers opening of voltage-gated Ca2+ channels
  • Ca2+ diffuses into axon terminal, triggers release of ACh by exocytosis
  • ACh diffuses across synaptic cleft, binds to ACh-gated Na+ channels, produces graded depolarization
  • Depolarization ends as ACh is broken down into acetate and choline by AChE
  • Axon terminal reabsorbs choline and uses it to synthesise new ACh