<aside> 💡 Excitable Membranes - Intro Neurophysiology

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1. Outline the roles of the various types of ions channels present in membranes of excitable cells

   

   • Passive
     1. Leakage/Non-gated
     2. Always open
     3. Found in all regions of a neuron
   • Chemical Gated
     1. Ligand gated
     2. Found in dendrites (post synaptic)
     3. Open in response to binding of specific neurotransmitter ex. ACh
   • Voltage Gated
     1. Opens/closes in response to physical changes in membrane potential (depolarization)
     2. Found in axon, open as a result of local currents
   • Mechanically Gated
     1. Opens/closes in response to physical deformation
     2. Sensory receptors ex. Nociceptors (pain sensors)
   • Ions diffuse quickly across membranes through channels following electrochemical gradients
   • Ion flow creates an electrical current and voltage changes across

2. Describe the functional role of the Na+/K+ pump

   • Function

     1. 3 Na+ bind
     2. ATP hydrolysis phosphorylates an internal domain, changes conformation
     3. 3Na+ released to ECF
     4. 2K+ ECF binds, bound phosphate group hydrolysed to Pi
     5. Return pump to original conformation, release K+ inside cells
     6. Result: low ICF Na+, high ICF K+

   • Role:

     1. Maintains resting membrane potential (-70mV)
     2. Resets ion concentrations so more APs can be sent
     3. Maintains osmotic homeostasis
     4. Secondary active transport
     5. Uses ~25% of brain’s energy

     

3. Explain the ionic basis for the resting membrane potential

   

   • Resting membrane potential = potential difference across membrane of resting cell
     • Na+ RMP = +66mV
     • Cl- RMP = -70mV
     • K+ RMP = -90mV
   • Approximately -70mV in neurons
   • Cytoplasmic side negative relative to extracellular side
   • Resting potential is as a result of:
     1. mainly due to differential permeability of membrane to Na+/K+

        1. K+ passive leak channels, more K+ efluxes than Na+ influxing

        2. More cations leak out, more negative charge
        3. Found all over neuron
     2. Negative ICF anions, proteins
     3. Ionic concentrations of ICF/ECF maintained by Na+/K+ ATPase
        1. Na+/K+ maintains higher ICF [K+], lower ICF [Na+]
        2. Loss of positive charge
   • Voltage gated Na+, K+ channels closed
     1. Na+ channel inactivation gate open
   • Small build-up of +ve charges on outer membrane surface, -ve charges on inner membrane surface

4. Apply the Nernst and Goldman equations to investigate parameters that alter membrane potential

   • Nernst equation

   • Goldman equation

5. Explain the ionic movements responsible for the phases of an action potential

   

   

   • Depolarization
     1. Depolarization = loss of polarity (cell goes from highly negative:-70mV to zero/slightly positive: +30mV)
     2. Once threshold reached (-55mV), voltage gated Na+ channels opens in axon
     3. Na+ influx, increasing number of positive ions within neuron
     4. Increase in membrane potential (up to around +30mV)
     5. Build-up of +ve charges along inner surface of membrane
     6. Absolute refractory period: (absolutely) cannot generate APs while transmitting (ensures one way)
   • Repolarization
     1. Inactivation gate of Na+ channel closes
     2. K+ channels open, K+ ions efflux
     3. Reduced number of positive ions; MP drops
     4. -ve charges build-up along inner surface of membrane
     5. Relative refractory period: can only transmit if signal is (relatively) high
   • Hyperpolarization
     1. K+ efflux continues (because K+ closes slower, and higer membrane permeablity to K+)
     2. Loss of positively charged ions, MP drops further
     3. MP drops below RMP (-90mV)
     4. -ve charges build-up along inner surface of membrane
     5. Relative refractory period, can only generate AP if signal strong enough
     6. Na+/K+ ATPase restores RMP

6. Describe the processes responsible for refractory periods and apply these to explain the mechanism for coding of stimulus intensity

   

   • Absolute refractory period
     1. Period which neuron (absolutely) cannot generate APs while transmitting (ensures one way)
     2. Depolarization and repolarization
        1. During depolarization: Na+ channels are already open, and cannot be opened more
        2. During repolarization: Na+ channel’s inactivation gates close, cannot open untill reset
     3. Ensures one-way (all or none) transmission of nerve impulses
   • Relative refractory period
   • Coding for stimulus

7. Explain how action potentials are propagated and describe the factors that affect conduction velocity

8. Describe the sequence of events in the process of synaptic neurotransmission

9. Outline the different types of synaptic potential evoked by neurotransmitters, and outline how they integrate in a functional network

10. Compare the processes involved in activation of ionotropic and metabotropic (GPCR) receptors

11. Outline the role of neurotransmitters, and alterations in GPCR function, in disease and responses to toxins