Electrical Signalling in Neurons (Part II) Flashcards
Why are firing patterns so important ?
The firing patterns dictates feeding behaviour. The response of hypothalamic neurons to food intake was shown to vary between mice (two example mice shown in the figure). This was correlated with their feeding behaviour, i.e. how much they eat and how long they eat.
Explain the family of Voltage-gated K+channels ?
- There are lots of different genes encoding VG K+ channels, and the family is divided into subfamilies that are called Kv1, Kv2.. based upon sequence similarity.
- Within subfamilies there are often several different members called Kv1.1, Kv1.2.. etc.
- They are structurally similar to one another and arose from the same ancestral gene as voltage-gated Na+ and voltage-gated Ca2+ channels.
How does the opening of KV channels affect the action potential wave form ?
An example of how opening of Kv channel speeds the rate of repolarisation of the action potential thereby shortening the duration.
The different subtypes show differences in ?
Their voltage-dependence and in their gating kinetics
What do these difference in their voltage-dependence and in their gating kinetics ?
These differences mean that they open and close at different times and contribute differently to the firing properties, e.g. some such as Kv1 and Kv4 will be more important in determining the interval between AP firing and others such as Kv2 and Kv3 the duration of the AP
The role of an ion channel in neuronal function will depend not only on its properties but also where it is ?
Targeted to
Voltage gated ion channels involved in the initiation and propagation of the AP are targeted to ?
The axon hillock (AIS) and the Nodes of Ranvier. Others are targeted to the pre-synaptic terminals to affect neurotransmitter release and others to the dendrites to regulate integration of synaptic inputs
What did Hodgkin and Huxley use and why ?
- Hodgkin and Huxley used tetrodotoxin (TTX) and tetraethylammonium (TEA) to dissect out the components of the current contributing to the total current in the squid giant axon
- The inward Na+ current was selectively blocked by TTX, obtained from the puffer fish. TTX binds to the pore with very high affinity
- The outward K+ current was blocked by TEA
Apamin (from Bee venom)
reveals the role of a KV channel in slowing the rate of firing of action potentials in?
Hippocampal neurons
It turns out that toxins from venomous animals commonly contain peptide toxins that target ion channels and this inactivates?
Their prey
- These toxins have proved very useful to neuroscientists to learn more about ion channel structure and function
No pharmacological agents are completely selective for?
Any one channel
The transmembrane topology of VG ion channels?
The genes encoding mammalian NaV and CaV channels encode polypeptides that are comprised of 4 domains each comprising 6 membrane spanning regions (so 24 TM regions in total). KV channels are comprised of just one domain with 6 TM regions and the channel complex consists of 4 subunits assembled into a tetramer
The topology of one subunit/domain of a VG ion channel ?
- 6 membrane spanning segments called S1 – S6
- S4 acts as the voltage sensor and contains a charged amino acid every third residue
- S5 – P-loop – S6 comprises the pore of the channel
Explain the selectivity filter pore?
The selectivity filter is the narrowest part of the pore where the permeating ion binds to the the channel and fully or partially dehydrates. Multiple ions occupy the pore at any moment in time
Explain the the voltage-dependence of activation/deactivation ?
The depolarising change in voltage across the membrane is sensed by the charged amino acids in the S4 segment and this moves outwards. The movement of these charged residues is coupled to the movement of the gate at the cytoplasmic side of the S6 segment, which opens the pore (activation). When the membrane potential hyperpolarises this process is reversed (deactivation)
