14 - Ion Channels Flashcards
Which ion concentrations are HIGHER INSIDE?
intracellular
K+
potassium
Types of Gated Ion Channels
Voltage-Gated
Respond to changes across membranes
Ligand-Gated
Either extracellular or intracellular ligand
Mechanicaly Gated
hair or hearing, we dont discuss
Activated Neuromuscular Junction Steps
After Nerve Impulse
-
Pre-synaptic Voltage gated Ca2+ Channel OPENS
- allows for Ca2+ to release acetylcholine
-
ACThbindsPost-synaptic ACTH gated cation channel
- allows Na+ to enter the muscle cell
-
Post-Synaptic Voltage-Gated Na+ Channel
- also lets Na+ enter the muscle cell
-
Ca2+ Gated Release channel
- releases Ca2+ from muscle’s sarcoplasmic reticulum
Describe how ion-transporters / pumps establish
electrochemical gradients + voltage potentials
across a membrane
Cell / Organelle membranes are barriers to charged ions
- Ion Transporters/pumps push ions against their gradient
-
Imbalance of ions across the membranes
- lead to ELECTROCHEMICAL GRADIENTS
- = Chemical + Electrical (gradient)
- lead to ELECTROCHEMICAL GRADIENTS
-
Imbalance of ions across the membranes
- Difference in BOTH solute concentation & charge
- across the membrane
INHIBITORY
Transmitter gated ion channels
CHLORINE
GABA- Gated Cl- Channels
glycine-gated Cl- Channels
Ion Channels Selectivity
Some ion channels are:
HIGHLY SELECTIVE & VERY SPECIFIC
only allow the transport of 1 specific ION, interact with side chains
Some ion channels allow for transport of VARIOUS ions
GABA-B Function
EXCITORY for what ion channels?
GPCR that regulates ion channels
K (out) channel
lets K+ leave membrane
Acetylcholine Receptor
(AChRs)
2 Types
5 Subunits in a ligand-gated channel
(2*Alpha - Beta - Delta - Gamma*middle)
2 primary types of AChRs
Nicotinic
Muscarinic
muscarine is much more POTENT = TOXIN, locks the channel
Photo of an action potential illustrating the rise and fall of membrane potential over time
PROPAGATION GOES TO THE RIGHT
but the order action potential wave order is to the left
Closed -> Open -> Inactivated –> repeat
STIMULUS -> Depolarized -> Repolarized
Three States of Ion Channels
Closed -> OPEN -> Inactive
-Polarized- (negative inside)
Closed
+DEpolarized+ (positive inside):
OPEN -> Inactive
Describe how ion-transporters / pumps
establish ion gradients
P-Type Pump
also F-Type/V-type Proton pump & ABC Transporter
-
ATP phosphorylation -> Conformational change
- allows to push IONS against the gradient
- Ex. 3Na+ / 2K+ Antiporter
- Na OUT
- typically high outside, so against its gradient
- K IN
- typically high INSIDE, so also against its gradient
- Na OUT
Uniport
Equal transport of
ONE molecule
Antiport
(type of coupled Transport)
2 molecules in the OPPOSITE DIRECTION
1 = transported molecule
1 = CO-Transported ION
Ex. 3Na/2K antiporter
Electrochemical Gradient
Chemical + Electrical Gradient
- Chemical:
- difference in solute concentration across a membrane
- Electrical:
- difference in charge across a membrane.
Describe how 3 activity states of voltage-gated ion channels propagates an ACTION POTENTIAL
Closed -> OPEN -> Inactive
(Voltage-gated Na+ channels)
-
STIMULUS –> leads to DEpolarization
-
Closed –> OPEN
- +ions+ are allowed to flow inside
- Action Potential propegated –> RIGHT
-
Closed –> OPEN
-
OPEN –> Inactive channel
- Keeps from action potential from pushing LEFT
- allows for the ion pumps to, re-establish the potential
- inside returns to -negative-
- = -Repolarization - Channel Closed
- inside returns to -negative-
- allows for the ion pumps to, re-establish the potential
Symport
(type of coupled Transport)
EQUAL transport (same direction)
of 2 Molecules
1 transported + 1 Co-transported ion
GABA-B Function
INHIBITORY for what ion channels?
GPCR that regulates ion channels
Calcium (IN) Channel
keeps Ca from entering cell
Adenyl Cyclase
inhibits AC from creating cAMP
Na+ / K+ Antiporter Steps
-
Na+ Loads
- Hydrolysis of ATP -> Phosphorylation of PUMP
- Conformational Change
- Hydrolysis of ATP -> Phosphorylation of PUMP
- Release of ADP leads to another Conformational Change
- Allows for binding of = K loads
- Na+ OUT leaves cell
- Allows for binding of = K loads
-
Phosphate is hydrolyzed
- -> Conformational change
-
K+ IN enters cell
- REPEAT
What is one drug that targets ion channels and alters their ability to respond to ligands or work as partial agonist to modulate channel activity
Varenicline (Chantix)
-
partial agonist of one subtype of:
-
Nicotinic Acetylcholine Receptor
- membrane-bound ligend-gated ion channel Na/K
-
Nicotinic Acetylcholine Receptor
Barbs / Steroids / BZD
+Agonist of GABAA Ion-Gated Channel
increases the influx of Cl- –> inhibits firing of action potential
GABA-A Antagonist
Types / Function
Stimulant Effect / Cause Convulsions
can be used to counteract large doses of Barbituates
PICROTOXIN
Understand that action potentials lead to release of neurotransmitters, like acetylcholine, at a
synapse, and realize that neurotransmitters are ligands whose receptors are ion channels in the post-synaptic cell.
- Action Potential propegated –> nerve terminal (SYNAPSE)
-
NT = Acetylcholine RELEASED from synaptic vesicles
-
ACTh -> synaptic cleft
- ACTh targets Transmitter gated ion channel
- ALLOWS FOR AP TO BE PROPEGATED TO THE NEXT AXON
- ACTh targets Transmitter gated ion channel
-
ACTh -> synaptic cleft
-
NT = Acetylcholine RELEASED from synaptic vesicles
3 States of Ligand-Gated Ion Channels
Occupied & Closed
(inactive until degraed or ligand is removed)
vvvvvv
Unoccupied & Closed
^V^V^(both ways)V^V^
Occupied & OPEN
P-Type Pumps
Maintain Ion Gradients & Require ATP
- Phosphorylated by ATP
- -> conformational change
- allows for ions to move against the ion gradient
- Na+ / Ca2+
- K+ / H+
- allows for ions to move against the ion gradient
- -> conformational change
y-Aminobutyric Acid
GABA
Inhibitory NT in CNS
Has 2 receptors:
GABAA, TYPE-A = Cl- Channel linked receptor
GABA<span>B</span>, Type B = GPCR that regulates ion channel
EXCITATORY
Transmitter-gated Ion Channels
GAS
Glutamiate-gated Ca2+ Channels
Acetylcholine-gated Cation Channels
Serotonin-Gated cation Channels
GABA-A Agonist
Types & Function
SEDATIVE / ANXIETY RELIEF
Cl- influx -> inhibition of firing new AP’s
Barbiturates
Steroids
Benzodiazepines
Patch-Clamp Recording
Used to Monitor / Isolate an ION CHANNEL
uses a micropipet to detach the patch of the membrane
to see the activity of ion channels
Ion Channel’s
Selectivity Filter & Vestibule
Some Ion channels are highly selective & very specific
-
Vestibule
- Large area that has water molecules that interacts with the various ions.
-
Selectivity Filter
-
STRIPS IONS of WATER
- only lets SPECIFIC ions pass through the channel
- specific alignment /interaction of side chains
-
STRIPS IONS of WATER
Na+ / K+ Antiporter
steps / function
3Na+ OUT Na is typically HIGH outside
2K+ IN K is typically low outside / high inside
(Against their chemical gradients)
to form ION GRADIENT
Conformational Change
Where are most ion channels located?
NODES OF RANVIER
Gaps between Glial Cells (schwann cells in PNS)
(insulation, sections of layers of myelin sheath)
Which ions are HIGHER OUTSIDE the Cell?
extracellular
Cations
Ca2+ > Na2+
(10,000x > 10-30x)
Anions:
Cl-
PSP
Post-Synaptic Potential
Frequency of AP’s depend on
STRENGTH OF SIGNAL
might need to reach a THRESHOLD for magnitude to occur
monitored by PATCH CLAMP
GABA-A Function
Cl- Channel-Linked Receptor
Influx of Cl- -> INHIBITS firing of new AP’s
Agonist produce sedative effects / relieve anxiety
BARBS / steroids / BZD
Antagonist -> stimulant / convulsant
Picrotoxin
