W6 - Ion channels Flashcards
How many genes encode K channels
70
what are the purpose of the K channels in the body
frequency and shape of action potentials
Secretion of hormones
Secretion of neurotransmitters
Membrane potential
What is the standard amount of K+ in a cell
150 mMOL
What is the extracellular amount of K+ at rest
2.5 mMOL
At rest what happens in response to the concentration gradient K+
due to electrochemical gradient K+ moves out of the cell into the extracellular fluid
What about Na+ and Ca2+ (electrochemical gradient
They have the opposite to K+ so move into the cell down the concentration gradient from the extra cellular fluid.
Describe the structure of K+ channel
There is a N (NH2) terminus and C (COOH) terminus located intracellularly
There are 6 subunits S1 - S6 which are connected across the membrane (transmembrane)
There is a gap between S5 and S6 which is where the K+ ion is conducted through the membrane
S4 has a positive charge so is believed to be sensitive to voltage.
What is an example of something that opens K+
Minoxidil opens the K+ channel and causes hyper polarization in smooth muscle cells, muscle relaxation and hence vasodilation.
What can minoxidil be used to treat
can be used to treat hypertension in combination with a diuretic and beta adrenoreceptor blocker
What type of channel is a sodium ion channel
voltage gated
How many alpha subunits makes up a sodium channel
one pore forming alpha subunit (which can be associated with either one or two beta subunits)
How many alpha subunits is a Potassium channel made up of
4 pore forming alpha subunits
what is the minimum amount of genes coding a sodium channel
at least 10
Describe the structure of a sodium channel
There is an amino terminus and a carboxyl terminus intracellularly
There are 6 Segments denoted s1 through to s6
S4 again is the voltage sensing subunit being positively charged
there is a gap between segment 5 and 6
While the transmembrane subunits they are connected to form the alphas subunit
What are the two terminus’s of the sodium channel
carboxyl and amino terminus
how many segments are there
6
what is the voltage sensing segment
4
why is s4 believed to be the voltage sensing segment
due to its positive charge
where do the ions move through
there is a gap between s5 and s6
What is an example of a drug that affect the sodium ion channel
lidocaine
what does lidocaine do
blocks voltage gated sodium channels
what is the primary target of lidocaine
Nav1.5 which is the main cardiac sodium channel
what is the indication of lidocaine
ventricular arrhythmias, especially after myocardial infarction in addition to local anaesthesia
what is myocardial infarction
heart attack
What type of channel is Ca2+
voltage gated ion channel
what do Ca2+ channels form
hetero oligomeric complexes
What is an oligomer
a polymer whose molecules consist of relatively few repeating units.
What is a hetero oligomer
Functional protein complexes formed by oligomerization of similar subunits.
Describe the Ca2+ hetero oligomeric complex
The α1 subunit is pore-forming and provides the extracellular binding site(s) for practically all agonists and antagonists.
What are the three families of Ca2+ channels
high voltage activated dihydropyridine sensitive channels
The high voltage activated dihydropyridine insensitive channels
low voltage activated channels
What does L type refer to
high voltage activated dihydropyridine sensitive channels
What does CaV1.x refer to
high voltage activated dihydropyridine sensitive channels
What does CaV2.x refer to
The high voltage activated dihydropyridine insensitive channels
What does T type refer to
low voltage activated channels
What does CaV3.x refer to
low voltage activated channels
what does alpha 2 delta 1 and 2 do
bind gabapentin and pregabalin
Describe the structure of a high voltage activated calcium channel
N terminus C terminus intracellularly similar to K+ and Na+
Contains a gamma and a beta subunit (low voltage activated does not have either of these)
Contains alpha 2 delta subunit
Contains 4 domains which consist of 6 transmembrane sections
as per the K+ and Na+ S4 is the voltage sensitive section
there is a gap between s5 and s6 which Ca2+ travels through
What two terminals does a Ca2+ channel have
NH2
CooH
What are the different subunits contained in a calcium channel
Alpha subunit
Beta subunit
Gamma Subunit
How many sections does a domain of an alpha subunit have
6
what is the voltage sensitive section of a domain of an alpha subunit
4
where does the ca2+ travel through
there is a gap between s5 and s6
what is a drug which effects the ca2+ channe
verapamil
what does verapamil do
blocks voltage gated Ca”+ channels (L type)
What effect does verapamil have
blocks calcium influx in myocardial and vascular smooth muscle cells.
Lead to a reduction in cardiac and VSm contraction
bringing about a dilation in coronary and systemic arteries
what is the indication of verapamil
supraventricular arrhythmias, angina, hypertension (dose and preparation dependent)
What channels effect epilepsy
K+
Ca2+
Na+
What channels effect diabetes
K+
Katp
What channels effect ataxia
K+
Ca2+
what is ataxia
People with ataxia lose muscle control in their arms and legs. This may lead to a lack of balance, coordination, and trouble walking. Ataxia may affect the fingers, hands, arms, legs, body, speech, and even eye movements.
What channels affect pain
Na+
Ca2+
What are ligand gated channels often known as
ionotropic receptors
what do ligand gated channels do
they link ligand binding to an ionic flux
How many subunits are ligand gated ion channels made up of
4-5
How many ACh receptors are there
2
What are the 6 receptor classes
nAChR Glutamate (ionotropic) 5HT3 Glycine GABAa ATP receptors (P2X)
What gated Ion is nAChR
Na+
What effect does Na+ have on the nAChR receptor
Excitatory
What gated ion channel is Glutamate
Na+
What effect does Na+ have on the Glutamate receptor
Excitatory
What gated ion channel is 5HT3
Na+
What effect does Na+ have on 5HT3
Excitatory
What gated ion channel is Glycine
Cl-
What effect does Cl - have on Glycine
inhibitory
what gated ion channel is GABAa
Cl-
what effect does Cl- have on GABAa
inhibitory
What type of ion channels is P2X
Na+
K+
Ca2+
Exceptionally CL
What are ligand gated ion channels
integral membrane proteins that contain a pore which allows the regulated flow of selected ions across the plasma membrane
what type of process is ion flux
passive
what is ion flux driven by
electrochemical gradient
what are the channels opened by
ligand binding that triggers a conformational change that results in the conducting state
What is the abbreviation of ligand gated ion channel
LGIC
What scale do LGIC’s mediate fast synaptic transmission
millisecond time scale
Where do LGIC’s mediate fast synaptic transmission
nervous system and somatic neuromuscular junction
what suggests that LGIC’s have additional functions
expression by non excitable cells
Describe the structure of a typical ligand gated channel
There is a Nh2 terminus and a cooh terminus extra cellularly
ACH binding site extracellularly near the Nh2 terminus
there are 5 repeating subunits
in each subunit there is TM2 which is the voltage sensitive
What are exceptions to the standard structure
Ach, Gaba and Glycine receptor channels
Glutamate receptor channels
ATP receptor channels
What drug can affect nAChR
Succinylcholine
What does it do
its a full agonist of the nAChR receptor activates the channel
what effect does Succinylcholine have
mimics the effects of ACh but is not subject to breakdown by AChE
Indication of Succinylcholine
Neuromuscular blocade for surgery
