Signalling in the nervous system L9 Flashcards
what is the nervous system
A complex network of interconnecting neurones
Neurones –electrically excitable cells which release neurotransmitters
what are the two types of signalling
- electrical: action potentials
- Site for drug action - chemical: neurotransmitters
what are the different types of neurones
sensory
- pseudo unipolar or bipolar
intermediate
- multipolar
motor
- multipolar
what features do all neurones have
- cell body
- dendrites
- axon hillock
- axon
- terminal
describe the permeability of the major ions
Na+: impermeable
K+: membrane is permeable (leak)
Cl-: membrane is permeable
A- (large anions): fixed inside
why may positive ions that are permeable not distribute equally
the concentration gradient (chemical force) is in competition with the electrical (ionic) force
the positive ions will be attracted to negative ions that are impermeable
Ions diffuse in accordance with the combined forces of concentration gradient and ionic gradient- electrochemical gradient
what are the two forces acting on ion flux
- Chemical gradient: ions move from areas of high concentration to areas of low concentration.
- Electrical gradient: ions move to areas of opposite charge.
what do the sum of chemical and electrical gradient determine
the net electrochemical gradient acting on an ion.
what does Na+/K+ ATPase do
pumps 3 Na+ out for 2 K+ in so Na is concentrated outside cell whilst K+ is concentrated inside the cell
describe movement of K+
The membrane is partly permeable to K+ ions and they tend to move down their concentration gradient
but they are forced to the inside by the ionic gradient and also transported by the Na+/K+ ATPase
describe the movement of Cl-
The membrane is partly permeable to Cl- ions and they tend to move down their concentration gradient into the cell
but they are forced to the outside by the ionic gradient
what is the composition of ions during resting membrane potential
Na and Cl outside cell
K and A- are inside cell
- inside is negative and outside is positive
how do neurones alter their membrane potentials
they have voltage gated channels that open when membrane reaches certain voltage
describe the action potential
- voltage gated Na+ channels open at -55mv (threshold)
- this allow more Na+ to enter causing rapid depolarisation
- membrane potential rises
- depolarisation - voltage gated Na channels become inactive after 1ms
- Na ions pumped out by Na/K ATPase
- membrane potential falls
- repolarisation - when membrane is slightly depolarised, voltage gated K+ channels open
- K goes out cell
- reduces membrane potential
- Movement of K+ is mainly responsible for speeding up repolarization - K+ channels close slowly
- Permeability to K+ is greater than at rest so K+ continues to leave the cell
- Membrane potential falls below RMP
- This is the ‘after hyperpolarization’
how does action potential propagate
saltatory conduction
what is refractory period
Because Na+ channels become inactivated after being activated they are refractory
Na+ channel cannot be opened again immediately
The AP propagates in only one direction
what is the physiological and pharmological significance of chemical signalling
- communication between neurones
- complex signalling-different response
- sites for drug action
give two types of neurotransmitters and examples
- monoamines
-Noradrenaline (NA)
-Dopamine (DA)
-5-HT (5-hydroxytryptamine) serotonin - amino acids
- glutamate
- GABA
what are the common features of neurotransmitters
synthesis
storage & release
interaction with target cell
termination of action
how are neurotransmitters synthesised
they are synthesised from a precursor by the action of enzyme
- DA synthesised from tyrosine by tyrosine hydroxylase and DOPA decarboxylase
how are neurotransmitters stored
stored in vesicles
- Ready for release
- Protected from metabolic enzymes
how are neurotransmitters released
neurotransmitters are released by exocytosis
this exocytosis is dependant on Ca+
how do neurotransmitters interact with receptors
receptors have specific neurotransmitter compliment
how is an action terminated
- reuptake
- High affinity reuptake removes transmitter from the synaptic cleft
- Intraneuronal metabolism then inactivates transmitter
- Monoamines & amino acids - metabolised
- ACH
- Extraneuronal metabolism inactivates transmitter
choline is recycled
what are 3 different types of receptors
- excitatory/ inhibitory
- ligand-gated ion channels
- G-protein linked
describe ligand-gated ion channels
Receptor with binding site linked directly to an ion channel
Binding to the receptor opens the channel
Channels are ion selective
Ions enter or leave the cell altering membrane potential
give neurotransmitter and the ligand gated ion channels that they bind to and it effect
NMDA (glutamate)
Nicotinic (ACh)
5-HT3
- Na (Ca) channel
- excitatory
GABAA
- Cl channels
- inhibitory
describe G-protein coupled receptor
neurotransmitter binds to receptor
alpha binds GTP so is active
then binds to other proteins
- adenylate cyclase (cAMP)
- phospholipase C (PIP3)
- GIRK (K+ ion channel)
how can drugs be used at synthesis
Transmitter synthesis may be increased or decreased by drugs
- synthesis enzyme inhibiting drugs
- decrease precursor availability
- false transmitters
how can drugs be used at storage
Vesicle disrupters cause initial increase in release then a decrease
how can drugs be used at release
Releasing agents cause non-impulse dependent release
Inhibitors of metabolic enzymes can increase transmitter in each vesicle
how can drugs be used at interaction with receptor
Receptor agonists, antagonists and modulators
how can drugs be terminated
Blockade of reuptake
- Causes build up of transmitter in the synaptic cleft
Inhibitors of metabolism
- Cause increase in level of transmitter in synaptic cleft
