week 6 Flashcards
define ion channels
hole in membrane - have a pore that once opens allows ions to flow in and out of the cell based on electrochemical & osmotic gradients
selectivity of ion channels
each channel is selective to the specific ion e.g., sodium, potassium, calcium
what five drivers move ions through channels
ions move toward electrochemical equilibrium through:
- electricity
- diffusion
- v-gated ion channels
- transporters
- passive
how to ions move through channels via electricity
= ions will move across a membrane if you introduce an electrical field. ions carry charge & pos NA will move towards negative terminal (inside cell) & likewise, neg CI will move towards pos terminal (outside cell)
ions moving through membrane via facilitated diffusion
= ions will move across the membrane passively provided channels are present & there is a concentration gradient i.e. more salt outside than in or vice versa
examples of channels that aren’t as selective/structured
- n-AChR conducts K, Na, Ca = 5-fold symmetry
2. chloride channel = 2 fold symmetry = ion pathway less obvious
three activations of ion channels
- voltage-gated
- ligand-gated ion channel
- G-protein coupled receptor
the steps of the movement of ions in a voltage gated sodium, potassium channel
- cell membrane depolarises
- sodium channels open = sodium rushes into the cell
- massive inward flow of charged sodium = changes
membrane to positive potential
- massive inward flow of charged sodium = changes
- causes potassium channels to open or activate = potassium starts flowing out of the cell carrying its positive charge with it = repolarising the membrane
- causes membrane to move back closer to resting
neg membrane potential
- causes membrane to move back closer to resting
what does the rapid movement of ions across the cell membrane cause
causes “action potentials” to propagate from one cell body, down axons to the synapse where they initiate release neurotransmitters
steps in APs & V-gated channels & transporters working together
step 1: membrane “resting” = sodium, potassium pump is closed, sodium & potassium channel closed (but still some passive movement)
step 2: rapid membrane depolarisation = sodium & potassium pump closed, sodium channel opens & sodium flows in
step 3: membrane repolarises = potassium channel opens, sodium channel starts closing (potassium flows out, sodium stops flowing)
step 4: membrane returns to rest = sodium & potassium pump open, sodium & potassium channel closed (sodium & potassium flows to equilibrium)
examples of functions of calcium channels
memory, neurotransmitter release, pace making action potentials, adrenaline/insulin secretion, contraction muscle tone
example of ion channel diseases
- cycstic fibrosis, epilepsy, cancer, heart disease
define channelopathies & 2 causes
= defects in ion channels
- genetic factors = mutations that lead to malfunction of ion channels can cause multiple diseases such as epilepsy
- environmental factors = continuous exposure to pain or certain drugs may cause channels to malfunction leading to chronic pain for example
How do calcium T-type regulate sodium, potassium driven action potentials
- injury occurs
- chemicals called cytokines are released
- this activates G-protein coupled receptors
- this activates protein kinases
- this hyperpolarises & activates T-type protein calcium channels
- the influx of highly positive calcium into the cell creates a deploarising event, triggering the sodium channel threshold causing the action potential to commence
how is ionic movement effected
by changes in the open/closed state as well as speed of open/closed state of channel (activation & inactivation kinetics)
channels activate & inactivate in response to
changes in membrane voltage
how can ionic movement be controlled
ion channel conformation can be controlled through drugs i.e. keep open/closed, active/inactive = bind to channel & restrict/reduce flow or opposite increase affinity
example of drugs that control ionic movement
- sodium channels e.g. AEPs, anaesthetics
2. calcium channel blockers e.g. DHPs, VDs
what does the movement of ions generate
electrical signals called action potentials that are tiny electrical units of information that connect neural circuits & instigate release of neurotransmitters
how much of hospital admission are estimated to be medicine -related causing significant morbidity & mortality
2-3%
1.4% likely to be due to adverse drug reaction
define therapeutic index
used to compare the therapeutic does to the toxic does of a pharmaceutical agent
= dose vs response in the population
define ED50
the drug dose that produces a therapeutic response in 50% of the population
define TD50
drug does that produces a toxic response in 50% of the population
equation for therapeutic index
TD50 divided by ED50
