M&C Neuroscience Flashcards
How do Kv1 and Kv3 compliment each other to enable fast AP firing? Give an example of a pathway that uses Kv1 and Kv3 channels for fast processing?
Kv1 raises threshold and Kv3 activate at high voltages and accelerate AP repolarisation. Kv1 is low voltage activated (activates from -65mV); Kv3 is high voltage activated (activates from -30mV)
Auditory processing - medial nucleus of the trapezioid body (MNTB)
What 3 complimentary experimental approaches are used to investigate native potassium currents?
- Neuron is voltage clamped and other voltage gated currents are blocked
- sodium channels are blocked with TTX
- calicum channels are blocked with cadmium (which blocks all 3 calcium channels) - Specific pharmacological agents are used as tools to distinguish between different Kv channels/families
- Immunohistochemistry used to identify the presence of Kv1 subunit protein in the membrane
What do dendrotoxin and TEA block?
DTX - Kv1
TEA - Kv3
How can you show that MNTB neurons contain high (Kv3) and low (Kv1) voltage activated potassium currents?
control I-V relationship
I-V relationship in the presence of 3mM TEA (Kv3 blocked) - curve more shallow than control after -30mV
I-V relationship in the presence of 10nM DTX-1 (Kv1 blocked) - curve even more shallow than TEA curve, almost no current at potential lower than -30mV (still currents due to Kv2s)
I-V relationship in the presence of 100nM DTX-1 - cell lost at -15mV
Describe immunohistochemistry
Detects antugens in cell by exploiting the principle of antibodies binding specifically to antigens in biological tissues
Visualisation: antibody conjugated to an enzyme that can catalyse a colout producing reagent OR antibody can be tagged with fluorophore
What are the functions of Kv1 channels in the brainstem auditory pathway?
Suppress firing of multiple APs by raising the threshold. Allows output AP train to accurately relay the pattern and timing of information across the brainstem - essential for sound localisation i.e. one presynaptic input = one postsynaptic output (only fires to strong inputs)
How are Kv3 channels opened and what is their function?
Open when depolarised to near 0mV (i.e. during AP)
Shorten APs by accelerating repolarisation
What phosphorylates Kv3 at ser503 and what does this do? What induces dephosphorylation of Kv3.1b?
PKC
Causes reduced Kv3 currents (allows Kv3 currents to be changed in response to the auditory environment) (Kv3.1b is basally phosphorylated at ser503 which reduces channel activity)
Sound stimulation induces Kv3.1b dephosphorylation via calcineurin
What is the function of Kv2?
Assists recovery of voltage gated sodium channels form inactivation
What makes up the brain stem?
Dicephalon, midbrain, pons, medulla
What are the functions of oligodendrocytes?
Insulation of axons, supply energy to axons (transport molecules from blood to neurons to overcome blood-brain barrier)
What are the functions of astrocytes?
Regulate concentration of ions and neurotransmitters in EC space Modulate synaptic signalling Promote formation of new synapses Supply energy to neurons Protects cells from oxidative stress
What are the functions of neurons?
Receive and process incoming signals of other neurons
Conveys APs over distances
May connect as many as 1000 postsynaptic neurons
What are homeobox proteins and their function?
DNA binding transcription factor that regulates subtype specific gene expression profiles (segment identity)
What do Hox genes do?
Pattern posterior embryos
