37 - Transporters Flashcards
Diazepam
Target WHAT? // Indication
Ligand-Gated GABA Channels
SEDATIVE
Target of SSRI’s
Fluoxetine / Sertraline / Citalopram
MoA
- *SERT**
- *Serotonin Transporter**
is involved in serotonin being
REUPTAKEN** –> back into the **PRE-synaptic neuron
INHIBITION
leads to MORE Serotonin in the Synaptic Cleft
VVVVV
Improve depression symptoms
What type of Transporter PROTEIN?
Water-filled –> extend across the cell membrane
GATED = closed or open
Involve Charged solutes
required to be transported rapidly across the membrane
CHANNELS
Ion Channels
Ex. of GATED channels:
Voltage-Gated Channels
open in response to magnitude of membrane potentials
Ligand-Gated channels
open in the presence of a specific ligand
How can ion channels discriminate between ions?
SELECTIVITY FILTER
these sites allow for the transporter protein to
FEEL IONS by
DEHYDRATION which Cost energy
but, Since the channels contain Oxygen-lined binding sites
these OFFSET the energy of Dehydration
important in distinguishing
Na+ vs K is the SIZE of the CAVITY
How are ION CHANNELS
CLASSIFIED?
Based on:
WHAT
leads to the Channel Opening/Closing
&
the TYPE of ION that is transported
A collection of protein domains that together create a water‐filled pore to allow the passage of ions through a cell membrane in response to: chemical stimuli, temperature changes, or mechanical forces
What is this?
ION CHANNEL
Excitable Cells & ION CHANNELS
Neurons / Muscle cells / Touch Receptors
are all excitable cells that use Ion channels to convert chemical/mechanical messages into:
ELECTRICAL SIGNALS
allow for RAPID ION MOVEMENT –> electrical signal
Self-propagting Electrical Signal
that can travel down the entire length of a cell
SERT = Serotonin Transporter
Facts:
ACTIVE TRANSPORTER = CARRIER
Belongs to the
NSS = NT Sodium SYMPORTER family
which also includes
Dopamine + NorEpinephrine Transporters
- *Na &** Serotinin
- -> REEnters the Pre-synpaptic cell
Physiological Necessity of
ION CHANNELS
generate ELECTRICAL SIGNALS
used to regulate CELL VOLUME
GRADIENTS
can be built across membranes using ion pumps
(lysosomes)
What type of TRANSPORT?
Thermodynamically favorable
Solutes transported from:
HIGH –> low conentrations
no ENERGY (ATP) required
PASSIVE TRANSPORT
DRUGS that target VOLTAGE-Gated Ion Channels
VOLTAGE GATED
- *Verapamil**
- *calcium** channels –> CCB –> HT
- *Lidocaine**
- *sodium** channel –> local anesthetic
Biosynthesis of Serotonin (5-HT)
Tryptophan = Trp
VVVV
Trp Hydroxylase + O2
VVVV
5-hydroxy-tryptophan — Decarboxylase
VVVV
5-HT = Serotonin
Example of DRUG that targets:
Neurotransmitter Carriers
transporters
SSRIs
Fluoxetine / Sertraline / Citalopram
Prozac / Zoloft / Celexa
INDICATION:
- *Depression / Anorexia / Bulimia**
- *OCD** / Panic+Anxiety Disorder
SSRI’s ONSET
Continue therapy for 4-6 weeks
SSRI’s have a slow onset
take for at least 8 weeks
Role of SEROTONIN:
5-HT
- *Serotonergic Signaling** influences
- *Neurologic processes** such as
Sleep / MOOD / cognition
Pain / hunger / aggression
Verapamil
Targets WHAT // Indicated for?
VOLTAGE GATED CALCIUM CHANNELS
CCB for HT
What MOLECULES are required in SERT?
- *SODIUM_ + _CHLORIDE** + K
- *Sodium Symporter**
conformational change
Na+ INFLUX along it’s concentration gradient
= driving force
- *Ion Channels**
- *Critical Roles in:**
Nerve / Muscle relaxation
COGNITION / Sensory Transduction
regulation of BLOOD PRESSURE
Cell Proliferation
Transporter Proteins
& why ther are needed
Drug targets:
Receptors > Enzymes > Transporters 15%
most common therapeutic action:
Anti-Hypertensive // Anti-arrhythmia
Facilitate the movement of specific substances:
Ions / Nutrients / Metabolites
across CELL MEMBRANES
Mediate:
Facilitated / Passive Transport
&
ACTIVE Transport
How do SSRI’s bind to SERT?
KNOW THIS ONE
SSRI’S BIND TWO SITES ON SERT
ALLOSTERIC SITE
which obstructs the release of drug bound to central site
LOCKS –> prevents/slows SSRI from leaving
Central Binding Site
block SERT in a configuration OPEN to the OUTSIDE to the neuron
prevents serotonin binding & further motion
Drug that targets Ligand-Gated Ion Channels
Varenicline = Chantix
acetylcholine‐gated ion channels
Partial Agonist for SMOKING CESSATION
- *Diazepam**
- *Gaba** channels –> sedative
Lidocaine & Bupivacaine
Target WHAT? // Indication
Voltage-Gated Sodium Channels
LOCAL ANESTHETIC
MECHANISM of SERT
SYMPORTER
which is driven by the Na+ influx along it’s concentration gradient
(Na is HIGH OUTSIDE –> wants to ENTER the cell)
- Open to outside of cell:
- Na & Serotonin & Cl
- Conformational change
- Opens INSIDE of cell
- Na + Serotonin enter the cell
-
K+ & Cl in the symporter
- K+ OUT
How does Varenicline help smoking cessation?
Chantix
Partial Agonist
of a AcetylCholine-Gated Ion Channel
VVVVV
Elicits a Moderate / Sustained INCREASE in DOPAMINE LEVELS
which causes a Reduction in craving
VVVVVV
SHIELDING the smoke from producing a
nicotine-induced DOPAMENIRGIC activation
NO REWARD SYSTEM FROM SMOKING
Varenicline
Target WHAT? // Indication
Partial Agonist
of LIGAND GATED ION CHANNEL
Smoking Cessation
CHANTIX
What type of TRANSPORT?
Thermodynamically UN-favorable
Solutes transported from:
low –> HIGH concentrations
requires ENERGY ATP
ACTIVE TRANSPORT
Proton pump
ION CHANNEL
FUNCTION
Gated & Water Filled PORES
that permit the FLUX of IONS down their
EC Potential Gradient = PASSIVE
Na / K / Cl / Ca
Na/Ca OUT
K IN
What type of Transporter PROTEIN?
undergo CONFORMATIONAL change
which dilivers solute to other side
SELECTIVITY of their solutes
that are permitted to enter or exit
CARRIER
Transporter Protein
Neurotransmitter Carrier
