Signalling in the nervous system Flashcards
Neuronal signaling definition
The transfer of information along and between neurones.
Electrical signalling definition
Cell body communicated with its terminuss using electrical impulses.
Action potential causes depolarization of the terminal and release of neurotransmitter.
Major ions that contribute to membrane potential
Na+
K+
Cl-
A- (Large anions)
Resting membrane potential
Cell membranes are impermeable to Na+.
Na+ is pumped out of the cell by Na+/K+ ATPase.
2 K+ ions pumped in for every 3 Na+ pumped out.
Na+ is concentrated outside the cell.
K+ is concentrated inside the cell.
Where are large anions (A-) found?
Trapped in the cell
What forces Cl- to stay out of the cell?
Electrical gradient.
What forced K+ to stay inside the cell?
Electrical gradient and Na+/K+ ATPase
At resting membrane potential where are the ions?
Na+ and Cl- are outside of the cell.
K+ and A- are inside of the cell.
The action potential - Movement of ions
If the membrane is slightly depolarized (-55mV), voltage-gated Na+ channels open so Na+ floods in. Voltage-gated K+ channels also open so K+ floods out. After 1ms Na+ channels inactivate (close) and K+ channels open and inactivate more slowly.
Propagation
Small area of membrane is depolarized.
Na+ moves into cell and is lost from external medium (less positive outside).
Local currents in adjacent sections.
Membrane reaches threshold for AP (-55mV).
Propagation of AP down the axon.
At axon hillock.
Na+ channels become inactivated, after being activated they are refractory.
Na+ channel cannot reopen again immediately.
Only propagates in one direction.
Neurotransmission - Physiological importance
Communication between neurones (Short distance/slow).
Complex signalling
Neurotransmission - Pharmacological importance
Site for drug action
Neurotransmitters: Monoamines
Noradrenaline (NA)
Dopamine (DA)
5-HT (5-hydroxytryptamine)
Acetylcholine (Ach)
Neurotransmitters: Amino acids
Glutamate
GABA (y-aminobuutyric acid)
Neurotransmitters: Synthesis
Synthesized from precursors by the action of enzymes.
EG DA synthesised from tyrosine by tyrosine hydroxylase and DOPA decarboxylase.
Neurotransmitter: Storage
Stored in vesicles ready for release. Protected from metabolic enzymes.
Neurotransmitter: Release
Depolarization of the terminal causes Ca2+ dependent exocytosis.
Voltage sensitive Ca2+ channels open.
Vesicles fuse with presynaptic membrane and empty into synaptic cleft.
Neurotransmitter: Termination (Re-uptake)
High affinity re-uptake removes transmitter from synaptic cleft.
Intraneuronal metabolism then inactivates transmitter.
Monoamines and amino acids.
Metabolica enzymes
Neurotransmitter: Termination (Metabolism)
Extraneuronal metabolism inactives transmitter, choline is recycled.
Metabolic enzymes.
Ach
Receptors used in neurotransmission.
Excitatory / inhibitory
Ligand-gated ion channels
G-protein coupled receptors
Neurotransmission (PHARMACOLOGY) - Synthesis
Transmitter synthesis may be increased or decreased by drugs.
False transmitter.
Precursor availability.
Enzyme inhibitors.
Neurotransmission (PHARMACOLOGY) - Storage and release
Vesicle disrupts causing initial increase in release, then a decrease.
Releasing agents cause non-impulse dependent release.
Inhibitors of intraneuronal metabolism enzymes can increase transmitter in each vessicle.
Neurotransmission (PHARMACOLOGY) - Interaction with target cell.
Receptor agonists, antagonists and modulators.
Each transmitter has many different receptor (sub)types.
These have different distributions and mediate different effects.
Neurotransmission is specialised at the receptor level.
Pharmacology can exploit this.
Neurotransmission (PHARMACOLOGY) - Termination
Blockage of uptake causes a build up of transmitter in the synaptic cleft.
Inhibitors of metabolism cause increase in level of transmitter in synaptic cleft.
