Ion channels as drug targets Flashcards
name some ligand gated ion channels
acetylcholine receptors - nicotinic
5-HT3 (serotonin)
GABA A
2 types of ion channel?
Ligand gated - ion channels open and close in response to binding of a ligand
voltage gated - respond to differences in membrane potential
what happens when ACh binds to nicotinic ach receptors?
causes formation of an ion pore, opens the channel. Sodium flows down its concentration gradient to cause depolarisation of the cell.
In muscle cells this means there is contraction
In neutrons it increases the probability of an AP firing
What is a drug that targets the nicotinic ACH receptor? (ligand gated ion channel)
succinylcholine - full agonist of the NACHR - mimics the effects of ACH but no subject to the breakdown by acetylcholine esterase - good for neuromuscular blockade during surgery
What is a drug that targets the 5-HT3 receptor? (ligand gated ion channel)
granisteron - antagonist of 5-HT3. 5-HT mediates the synaptic transmission to the medullary vomiting centre. So granisteron stops the signal being sent - for vomiting and nausea induced by cytotoxic drugs in chemotherapy
What is a drug that targets the GABA A receptor (ligand gated ion channel)
Diazepam = full agonist of the GABA a receptor - enhances its activity. For short term use in anxiety, insomnia, muscle spasms.
What ions are involved in: nACH receptors gluatamate receptors (ionotropic) 5-HT3 GABA -A Glycine
How fast is the transmission of these?
nACH = Na+ Glutamate = Na+ 5HT3 = Na+ GABA A = Cl- Glycine = Cl-
Fast synaptic transmission = physiological function
What are potassium channels involved in?
Frequency and shape of action potentials
secretion of hormones
secretion of neurotransmitters
membrane potentials
When potassium channels are opened (voltage gated) - where does the potassium flow?
From inside to outside of the cell (because concentration is higher intracellularly so moves out)
Name a drug involved in K+ channels
Minoxidil = opens K+ channels, efflux of K+ from the cell causing hyperpolarisation in smooth muscle cells. This causes relaxation and vasodilation. Used for hypertension in combination with a diuretic and beta-adrenceptor blocker
Where are Na channels present?
In the membrane of most excitable cells. (underlying action potentials). NOTE: sodium flows into the cell
Examples of voltage gated ion channels
K+, Na+, Ca2+ channels, TRP
Example of a drug acting on Na channels?
Lidocaine - it blocks the voltage gated sodium channels. There are 3 targets = Nav1.5, Nav1.7, Nav1.9. But the primary target for lidocaine is the Nav1.5 which is the main cardiac Na+ channel = used for ventricular arrhythmias especially after MI
Where are Ca channels present?
In the membrane of most excitable cells.- flows into the cell
what are the 3 families of Ca channels?
- The high voltage activated dihydropyridine sensitive = L-type channels = Cav1.x (open at high voltage)
- The high voltage activated dihydropyridine insensitive Cav2.x channels
- The low voltage activated (T-type) Cav3.v channels
