Functional roles of TRP, Cl, Connexins & other channels Flashcards
Discuss TRP channels
TRANSIENT R POTENTIAL (TRP)
-mediates light perception in fly eye
- tetrameric
- 6 TM domains per subunit
- Generate signals by DEPOL. & Ca entry
- Diverse structures & functions, but linked via PLC
What are some functions of TRP channels (in general)?
SOMATOSENSATION
- mechano-
- proprio-
- thermoception
-Nociception:
TRPV1
TRPM8
TRPA1
Discuss the properties of TRPV1
Venom contains toxins that modulate R/channel function to produce:
-shock
-paralysis
-death
(with ACUTE PAIN & NEUROGENIC INFLAM.)
Earth tiger toxin (DkTx) binds to TRPV1, & is an IRREVERSIBLE AGONIST!
Discuss the properties of TRPM8
Activated by MENTHOL and thermal COLD STIM. (synergistic)
What do TRPM8-deficient animals show?
No preference for warm vs cold
What is important in terms of TRP channel ANTAGONISTS?
May emerge as next generation analgesics
Discuss the properties of TRPA1
Detector of CHEM. IRRITANTS & inflame. factors
Activated by pungent agents from mustard (wasabi) and allium (garlic)
Why may TRP channels be potential therapeutic targets?
i.e. Block actions of inflame. agents without altering basal heat sensitivity
What are Cl channels?
“leak” anion (-) channels that accompany cation (+) channels
Name some classes of Cl channels
Cystic Fibrosis Transmembrane Regulator (CFTR)
Voltage-g (ClC)
Ca- Activated (CaCC)
Ligand-g (GABA & GLYCINE Rs)
What do Cystic Fibrosis and Myotonia have in common?
Inherited Cl- channel mutations
What is cystic fibrosis?
Lung pathology from DECREASED Cl- & bicarb. secretion from submucosal glands
THUS, viscous acidic airway surface liquid (that promotes bacteria colonisation)
What is myotonia?
ClC-1 provides the Cl-conductance in SKELETAL MUSCLE, assisting repolarisation after the AP
Inherited mutation in ClC-1 channels!
-exaggerated muscle contraction occur in response to normal stim.
DIscuss CaCC channels?
Slowly activated by depolarisation (Cav Ca entry)
Diverse functions:
- fertilisation
- olfaction
- smooth m. contraction
- sensory signal transduction
Regulated by Ca directly, or Ca modulated kinases
What are connexion channels?
GAP JUNCTIONS!
(Electrical synapses)
- 6 subunits per channel
- Developmental uncoupling overlaps with period of formation of chem. synapses & an increase in synaptic activity (NMDA Rs)
What do electrical synapses allow?
Bidirectional communication
What effect do gap junctions have in sub-lethal injury?
Gap junction coupling may assist NEURONAL SURIVAL
-by promoting SPREAD OF PRO-SURVIVAL SIGNALS
What effect do gap junctions have in severe brain injury?
Enable SPREAD OF PATHOLOGICAL CONDITIONS
- causing neuronal death
e. g. excitotoxic Ca
Discuss inward rectifiers
PLC cascade alters activity of Kir channels, creating the electrical response
2 TRANSMEM. DOMAINS (tetrameric channel)
-GPCRs generate EPSPs BY DECREASING ACTIVITY OF Kir CHANNELS, resulting in increase in excitation of the neuron!
