Ion Channels Flashcards
What are Specialised Functions of Ion Channels?
- Mediate the generation, conduction and transmission of electrical signals in the nervous system
- Control release of neurotransmitters and hormonse
- Initiate muscle contraction
- Transfer small molecules between cells
- Mediate fluid transport in secretory cells
- Control motility of growing and migrating cells
- Provide selective permeability properties important for various intracellular organelles
How to Ion Channels allow Polar Molecules to Pass the Cell Membrane?
- Ion channels allow ions to diffuse across the cell membrane as they cannot diffuse across the hydrophobic barrier ofthe lipid bilayer
- Tese ion channels form an internal hole (channel) surrounded by charged amino acid residues that are positioned inside the channel to allow polar molecules to pass
What is the importance of Ion Gradients?
- Ion gradients drive the process
- ions cannot pass the membrane by themselves
What is the difference between Ion Pumps and Ion Channels?
Ion Channels: Transport down the concentration gradient (simple diffusion - no energy)
Ion Pumps: Transport against the gradient (active transport - need ATP)
Describe the Specificity of Ion Channels
- Selectively permeable to specific ions
- Anion Permeable: Cl-
- Cation Permeable: Na+, K+, Ca2+
- Major regulation of ion channel activity is related to their opening and closing
What are the Four Ways of Ion Channel Binding?
- Voltage-gated
- A change in membrane potential opens ion channel
- Ligand-gated
- Ligand binds to ion channel
- Phosphorylation-gated
- Phosphate attaches to ion channel
- Stretch or pressure-gated
- A stretch in ion channel opens the ion channel
After binding, channel opens, allowing molecules in/out
How do poisons and drugs affect ion channel function?
- Most of these agents close the channel
- Some compounds bind to the same site at which the endogenous gating ligand normally binds and thereby prevent the activator from exerting its usual effect
- Other exogenous substances act in a non-competitive manner and affect normal gating mechanism without directly interacting with a ligand-binding site
What is GABA mechanism of action?
- Main inhibitory transmitter in the brain
- Entrance of positive charges (e.g. Na+) activates neuron (depolarisation)
- Entrance of negative charges (e.g. Cl-) counteracts this process and inactivates neuron (hyperpolarisation)
- GABA suppresses CNS activity
Know GABAs channel structure and function
- Consists of 5 subunits arranged around a central pore
- GABA causes this receptor to open
- Once bound to GABA, channel changes conformation, opening the pore causing Cl- to enter nerve
- Effect is reducing the acitivity of the neuron
Mechanism of Nerve Impulse Propagation
- As electrical impulses travel through neurons, there is a series of membrane potential shifts
- These shifts are due to the movement of Na+ and K+ ions across the membrane
- A stimulus strong enough will initiate a nerve impulse which leads to an action potential
- MECHANISM:
- Resting stage
- Threshold
- Depolarisation
- Repolarisation
- Refractory Period
- Resting Stage
Nerve Impulse Propagation IN DETAIL
- Resting Stage
- Na+ and K+ voltage-gated channels are closed
- Membrane not permeable to these ions
- Resting membrane Potential: -70mV
- Threshold
- A stimulus triggers opening of some Na+ channels and Na+ flow into the neuron
- If membrane potential reaches -55mV: action potential initiated
- Depolarisation
- Membrane becomes permeable to Na+, all Na+ channels open, Na+ rushes into neuron
- Inside of cell becomes more positive: +30mV at peak
- Repolarisation
- When depolarisation peaks at +30mV, potassium voltage-gated channels open, K+ rush out
- Na+ gates begin closing, inside of cell becomes negative, resting potential at -70mV is restored
- Refractory Period
- At -70mV all Na+ and K+ channels close, membrane potential < resting potential, Na+K+ pump actively pump Na+&K+ back across the membrane until resting state is re-established
- Resting State
- Re-establishment of resting state allows the conduction of another impuse
What is the complex regulation of GABAa channels and what are the drug-drug interactions relevant to GABAa channel?
- All of these molecules bind to different sites
- Most are positive allosteric modulators since they activate function of the channel by improving its confirmation
- All of these activators suppress CNS function
- If used together, could create dangerously strong suppression of CNS, creating either cardiac or respiratory arrest
What are allosteric modulators?
A substance which indirectly influence the effects of a receptor agonist or inverse agonist at its receptor protein target
What are positive allosteric modulators?
Bind to allosteric sites on GABAa channel causing an indirect increase in Cl- conductance
What are negative allosteric modulators?
Bind to an allosteric site on the receptor causing an indirect decrease in Cl- conductance
