1 Postural Control in Multiple Sclerosis: Stability and Complexity Analyses!Neural signals: membrane potentials and transmission! University of Massachusetts Amherst Department of Kinesiology Questions ① Are neurons good conductors? ② What type of electrical signals do neurons exhibit? ③ How do nerve cells use ions to generate electrical potential? ④ How does long distance signaling occur through action potentials? ⑤ How does myelination increase conduction velocity? ⑥ How does the breakdown of myelination affect people with Multiple Sclerosis? Question 1: Are neurons good conductors? Axonal current depends on how good its insulation is (the resistance of the axon membrane (RM)) and how much resistance is offered to currents flowing longitudinally through the axoplasm (the longitudinal resistance of the axoplasm (RL)). Question 1: Are neurons good conductors? Exponential decline in voltage as a function of distance along the axon. λ is the space constant: distance at which voltage drops 1/e ~ to 37% - Telephone wires – hundreds of miles - Nerves: ~ 4mm2 Types of neuronal electrical signals • Receptor potentials • Synaptic potentials • Action potentials Question 2: What type of electrical signals do neurons exhibit? Figure 2.1 Types of neuronal electrical signals (Part 1) Resting membrane potential Hyperpolarization of cone stimulated with different amounts of light Receptor potential: amplitude graded in proportion to stimulus strength Types of neuronal electrical signals (Part 2) Hippocampus Spinal networks (central pattern generators –CPG)3 Summation of postsynaptic potentials (Part 1) Types of neuronal electrical signals (Part 3) Motor Neuron AP AP: “booster system”; neurons are poor conductors Recording passive and active electrical signals in a nerve cell (Part 1) Recording passive and active electrical signals in a nerve cell (Part 2)4 Action Potential Features • Arises when membrane potential exceeds threshold (~ -50 mV) • Very brief: ~ 1 ms; from – to + • Magnitude the same: all or none • Frequency of AP encodes intensity of stimulus: intensity  then frequency AP  Generation of electrical signals Question 3: How do nerve cells use ions to generate electrical potential?  Electrical potentials are generated across membranes of neurons because:  Differences in concentration of ions (passive)  Active transport (ATP- sodium pump)  Selective permeability (ion channels) Active transport – the sodium pump Sodium pump. It swaps Na ions on the inside of a membrane with K ions on the outside of a membrane (three Na ions for two K ions). It is an active transport and uses adenosine triphosphate ATP). Without it cell would draw water and swell/burst Requires energy: ~ 20% resting energy Immediately available (unlike glycogen,fat)5 Membrane permeability No permeability Permeable to K+ Axonal membrane at at rest slightly permeable to K+ • Electrochemical equilibrium: balance between two opposing forces –  Concentration gradient that causes K+ Efflux  Electrical gradient: stops K+ efflux • Predicted by Nernst Equation: (z=valence or electrical charge; [x] is concentration) ! Ex=58zlog[X ]2[X ]1• Electrochemical equilibrium - resting potential:  (1) efflux of K+ due to concentration gradient  (2) this efflux will create electrical gradient (+) that impedes further flow of K+  Resting potential: -58 because [K+] higher inside – flows out – making inside negative Permeability to multiple ions Permeability to multiple ions6 • Multiple ions: Electrochemical equilibrium predicted by Goldman Equation: (Vm=voltage across membrane; [k] is concentration; and P is permeability) ! Vm =Pk[K]2+ PNa[Na]2Pk[K]1+ PNa[Na]1 Resting and action potentials arise from differential permeability to ions (Top) Permeability changes of sodium and potassium associated with action potential. (Bottom) Membrane potential changes as a result of permeability changes of sodium and potassium. Questions Question 4: How does long distance signaling occur through action potentials? Passive flow:  propagation 1-2 mm  decays over distance (leaks out) Action potential:  propagation 1+ meter!  amplitude constant; but slows down7 Passive current flow in an axon (Part 1) Propagation of an action potential Action potential conduction requires both active and passive current flow (Part 1) active passive 5 1 3 4 2 Action potential conduction requires both active and passive current flow (Part 2) ① Action potential – Na+ channels open ② Some depolarizing current passively flows down axon ③ Depolarization spreads ④ Upstream permeability changes- AP stops – refractory ⑤ Repeat of process8 Action Potential • Action potential (AP) propagation requires both active and passive current flow • After AP the neuron is ʻrefractoryʼ:  Prevents AP from flowing backwards  Upper limit on frequency of firing in neuron Questions Question 5: How does myelination increase conduction velocity? If only passive flow:  in conduction velocity through  in diameter only! Myelination: electrical ʻinsulationʼ unmyelinated: 0.5-10 m/s (~ 3 mph) myelinated: 150 m/s (~340 mph) Insulator: avoids leaking; speeds up; reduces amount of APʼs (time consuming) Saltatory action potential conduction along a myelinated axon (Part 2) Questions Question 6: How does the breakdown of myelination affect people with Multiple Sclerosis?9 Multiple Sclerosis (MS) • Auto-immune disease  Central Nervous System  T-cell attacking myelin protein  Normal nerve  Myelin sheath acts to insulate nerve conduction  Nerve affected by MS  Disruption of nerve conduction due to exposed axons  Cross-talk between affected neurons Canadian Network of MS Clinics American Academy of Family Physicians Symptoms of MS: Multiple Systems Affected Bladder dysfunction Bowel dysfunction Sexual dysfunction Changes in cognitive function Depression Other emotional changes Dizziness and vertigo Vision problems Muscle Weakness Spasticity Abnormal sensations Pain Symptomatic Fatigue Difficulty in walking Balance problems Questions ① Are neurons good conductors? ② What type of electrical signals do neurons exhibit? ③ How do nerve cells use ions to generate