Channels Flashcards
What facilitates the movement of ions across the membrane?
- Ion channels facilitate the movement of ions across the membrane
- However, membrane potential will influence direction of ion flow
Describe the movement of ions when the cell is subject to standard equilibrium conditions and at resting membrane potential and why this occurs
• When a cell is subject to standard equilibrium conditions and at resting membrane potential (about -60 mV)
o Large potassium gradient
High potassium concentration inside the cell (around 140 mM) vs low potassium concentration outside the cell (around 5 mM)
When a potassium channel is open, the potassium will flow from inside the cell to outside the cell
o Large sodium gradient
High sodium concentration outside the cell (around 130 mM) vs low potassium concentration inside the cell (around 10 mM)
When a sodium channel is open, the sodium will flow from outside the cell to inside the cell
o Calcium gradient
Calcium is dynamic inside the cell (nM when cell is resting, uM when cell is activated) vs higher calcium concentration outside the cell (1-2 mM)
When a calcium channel is open, the calcium will flow from outside the cell to inside the cell
o Large chloride gradient
High chloride concentration outside the cell (around 105 mM) vs low chloride concentration inside the cell (10 mM)
When a chloride channel is open, the chloride will flow from outside the cell to inside the cell
o There are large impermeant anions in the cytoplasm (these come from proteins and RNA)
o Sodium/Potassium ATPase channel will pump 2 K+ into the cell for each 3 Na+ pumped out of the cell
The energy used for this is derived from the hydrolysis of ATP
Sets up gradient that allows ions to move and respond to physiological processes
Describe what voltage gated ion channels (VGICs) are present in the dendrites of a neuron
• Dendrites
o Proton gated ion channels (HCN)
o Potassium gated ion channels (4.2, 3 and 2.1)
o Calcium channels
Describe what voltage gated ion channels (VGICs) are present in the axon hillock of a neuron
• Axon hillock
o Voltage dependent sodium channels
o Cyclic nucleotide-gated ion channels
o Acid-sensitive ions channels
Describe what voltage gated ion channels (VGICs) are present in the nodes of ranvier of a neuron
• Nodes of Ranvier o Voltage-dependent potassium channels Prior to the node and at the node o Voltage-dependent sodium channels At the node
Describe what voltage gated ion channels (VGICs) are present in the pre-synaptic of a neuron
• Pre-synaptic terminal o Voltage-dependent sodium channels o Voltage-dependent potassium channels o Calcium channels Trigger neurotransmitter release in the terminal to stimulate post-synaptic membrane
What are the roles of Kv and Nav channels in propagating the action potential?
• Nav opens in response to depolarization of the membrane potential
• Inward current due to the influx of Na+ causes further depolarization
o Nav will spontaneously inactivate after being open for 1-2 msec
• Depolarization also causes opening of Kv channels
• K+ ions flow out of the cell
o Speeds up the rate of depolarisation- causes the membrane potential to overshoot the resting state
o A diversity of Kv channels allows for variation in the duration of the action potential and the neuron’s rate of firing
Describe the format for voltage-gated ion channel nomenclature
• Formula: Xy0 o Where X is the ion that permeates the channel o Where y is the description of the channel/how the channel is activated o Where 0 is the subtype of the class of channel
Describe the voltage-gated ion channel family
• 143 members of the family in 7 major groups o Two major families Potassium channels TRP channels o Smaller families include Sodium channels • 9 major subtypes Calcium channels • 3 major subtypes CNG channels HCN channels TPC channels
What is the Nav1.7 channel, what is it expressed in, what is the impact of mutations in this channel, why is it an appealing drug target and what drugs are being developed for it?
• Mutations in Nav1.7 causes a complete loss of Na+ channel function and hence an inability to sense pain
• Nav1.7 is exclusively expressed by sensory neurones and so is a potential target for drugs to treat pain
• Selectivity for Nav 1.7 is critical because effects on related Nav channels would be fatal
• There are a number of pharmaceutical companies and academics working on developing selective Nav1.7 inhibitors but none of these drugs are on the market
o PF-05089771 (Pfizer)
o Monoclonal antibodies (Duke university)
o Tarantula toxins (peptides) are selective Nav1.7 inhibitors
University of Queensland and USYD
What is the purpose of Kv channels?
• Kv channels- large family with diverse functions
o Stabilising force
Setting the cells resting membrane potential
Repolarizing the cell after an action potential
Controlling the cell’s rate of firing and shape of the action potential
Do Kv channels always have 6 transmembrane domains?
No.
6 transmembrane K+ channels and 2 transmembrane K+ channels
What are the 4 main classes of Kv channels?
- Delayed rectifiers
- A-type channels
- Ca2+-activated K+ channels (KCa)
- Inward rectifiers
What is the purpose of Kv delayed rectifier channels?
• Delayed rectifiers- delayed activation after depolarization and inactivate slowly- facilitate repolarization
What is the purpose of A type channels?
• A-type channels transiently activated when a cell is depolarized after a period of hyperpolarization- decreases firing frequency
What is the purpose of Ca2+-activated K+ channels (KCa)?
• Ca2+-activated K+ channels (KCa)- respond to Ca2+, remain open for prolonged period- prolong hyperpolarization
o Open in response to binding of Ca2+- after depolarization induced Ca2+ entry
o Remain open for a long period (about a few seconds)
o Cause “long after hyperpolarization”- hyperpolarization after an action potential-can slow the rate of firing of action potentials
What is the purpose of inward rectifier channels?
• Inward rectifiers- G proteins can regulate their activity (GIRKs)
What is the molarity of extracellular neuron calcium?
1.5mM
What is the molarity of intracellular neuron calcium?
• Intracellular Ca2+ is 0.1-0.2 uM but may rise to 100 uM after opening of Ca2+ channels
What can calcium entry in a neuron trigger?
• Ca2+ entry can trigger many intracellular processes o Muscle contraction o Neurotransmitter release o Activation of second messenger systems o Alteration in gene expression o Apoptosis (cell death) o Depolarization- Ca2+ spikes
What calcium channels are classified as L type?
Cav1.1- 1.4
What calcium channels are classified as P/Q type?
Cav 2.1
What calcium channels are classified as N type?
Cav 2.2
What calcium channels are classified as R type?
Cav 2.3