Cellular Organisation of the Nervous System Flashcards
What is the most common type of glial cell within the brain ?
Astrocytes.
What cells are damaged in multiple sclerosis ?
Oligodendrocytes and Schwann cells are Responsible for myelin sheaths
CNS: oligodendrocytes
Myelinate multiple axons
PNS: Schwann cells
Myelinate single axon
Multiple sclerosis:
Autoimmune disorder
Targets myelin and myelin-creating cells
What is the immune cell within the brain ?
Microglia.
CNS immune cells
Normally exist in ramified form monitoring CNS; small soma and processes
Activated into phagocytic form – functions similar to peripheral phagocytic immune cells
If needed for severe immune response, the BBB can be broken down and monocytes recruited to assist in immune response
Inflammation within the brain - chronic inflammatory reponse
Dangerous!!
Epilepsy
Brain injury
Schizophrenia
Summaries nuerons
Summarise Glia
What is the electrical charge of a cell ?
-70mv
What are the 4 major ions which move in and out of the cells that cause the electrical status of a cell ?
K+
NA+
CA2+
CL-
What are gating systems ?
Specialised membrane proteins to allow ions to move across membrane
Numerous gating systems:
Leak channels
Ligand-gated (often receptors)
Voltage-gated
Mechanically gated
Ion channel activity can be modulated by intracellular signals
Explain the Action potential
Threshold: cell must be depolarised to open voltage gated channels (~ -50mV)
Depolarisation: Voltage-gated sodium channels open; gNa ↑. “All or nothing”
Overshoot: Membrane potential more determined by Na+ than K+; Vm goes more positive than 0mV.
Repolarisation: Voltage-gated sodium channels inactivated, voltage gated potassium channels open. Vm returns towards K+.
Undershoot: Voltage gated potassium channels remain open. gK higher than cell at rest: cell hyperpolarised.
All voltage gated channels closed – cell returns to RMP (K+ leak currents)
Explain refractory potential
Absolute refractory period:
VG Na+ channels inactivated. Another ACTION POTENTIAL CANNOT be generated.
Relative refractory period:
VG Na+ channels closed.
VG K+ channels still open and hyperpolarise membrane – harder to depolarise to threshold.
Explain Axonal Propagation
AP propagates down the axon as Na+ induced depolarised spreads.
APs are unidirectional:
Inactivation of Na+ channels and hyperpolarisation by K+ prevents the AP going backwards
Explain the function of Myelin
Electrical insulator – fatty layers have high resistance
Forms in discrete, separate bands along axons
Gaps between myelin sheathes called “nodes of Ranvier”. These nodes have very high concentrations of ion channels
Electrical signals “jump” from node to node – salutatory conduction
Explain Saltatory conduction
Depolarisation causes positively charged region of axon
Positive charge propagates towards more negative region of axon
Minimal leak, therefore very fast
At next node, depolarisation causes explosive opening of Na+ channels, and so on
Explain Multiple Sclerosis
Immune-mediated disorder involving destruction of myelin producing cells in brain and spinal cord.
Propagation of APs severely degraded or
slowed
Damage / death of myelin producing cells
Demyelination damages and may kill neurones
Devastating neurological consequences:
Muscle weakness
Loss of co-ordination
Loss of sensation
Visual disturbance
Importance of Ion Homestasis
Loss of normal resting membrane potential (Na+ / K+) = cellular dysfunction, inability to generate electrical signals
Sustained, high intracellular Ca2+ concentrations are cytotoxic
THIS IS AGAINST CONCENTRATION GRADIENT USING ATP.
The most important is the sodium – potassium exchanger (a.k.a. Na+ / K+ ATPase) which pumps 2 K+ in and 3 Na+ out. !!!!!!
What is the most important ion transported ?
Sodium - potassium exchanger
Brain is ~2% of the body by weight but uses ~20% of its energy consumption at rest.
> 50% of the brain’s energy requirement is powering the Na+ / K+ ATPase!
No energy reserves (fat / glycogen) in brain – THEREFORE WHEN THINGS GO WRONG THEY GO WRONG VERY QUICKLY.
Ion imbalance disorders
Neuronal & neuromuscular effects of electrolye disorders (e.g. hyperkalaemia, hyponatraemia)
Cortical spreading depression:
Waves of high extracellular K+ and depolarisation
Observed in several conditions e.g. stroke and migraine
Loss of calcium homeostasis
Major contributor to cell death and neurodegeneration
Explain Skeletal Muscle Innervation
Motor neurones from spine
Axons bundled together in nerves
Innervate muscle fibres
No gap junctions in skeletal muscle (unlike smooth and cardiac muscle); APs not passed to nearby cells.
The postsynaptic receptors at the neuromuscular junction are nicotinic acetylcholine receptors (nAChRs)
nAChRs depolarises muscle cell – muscle AP (VG Na)
Opens VG Ca2+ channels
Calcium induced calcium release from sarcoplasmic reticulum via ryanodine receptors = muscle contraction
Explain Inotropic ligand-gated ion channel
Ionotropic
Nicotinic acetylcholine receptor is classic example
Cation channels:
Na+ influx → depolarisation
(Some can have permeability to K+ and Ca2+ )
Explain GABAa Recpetor
Main CL- channel
Ionotropic
Inhibitory anion channel
Cl- influx → hyperpolarisation
Makes it less excitable
Explain Gs proteins
Stimulate adenylate cyclase
(↑ cAMP / PKA)
Increase nuerotrasmitter relase and excitability ?
Explain Gi protein
Inhibit adenylate cyclase
(↓ cAMP / PKA)
This means decreased activity of nueron and calcium entry.
Explain Gq protein
Activate phospholipase C
(↑PKC, ↑[Ca2+]i)
This increases the amount of calcium.
Explain Go proteins
Enhance K+ efflux
Inhibit Ca2+ entry
Less active
What are the main numerotrasmitters of the brain ?
STAR MEANS EXTREMELT IMPORTANT.
