Welcome to 632

1. Welcome to 632 Nerve Muscle and Movement Chris Elliott - cje2@york.ac.uk Sean Sweeney sts1@york.ac.uk John Sparrow - jcs1@york.ac.uk Web page: http://biolpc22.york.ac.uk/632/

2. Course Overview • Lectures • Chris 2 : Nerve and Synapse • Sean 2: Synapse development • Chris 2: Channels • John 4: Muscle • Chris 4: Movement

3. Nerve & brain lectures • In B006 • Nerve 1 Ionic basis of Resting and Action potentials 2 Mechanism of synaptic actions and neuromodulation 3 The Patch clamp approach to Neurobiology 4 Effect of Insecticides on Neural function

4. Movement lectures • Neural Control of singing and hearing in insects • Locomotion • Types & Principles of locomotion • Walking running & jumping • Swimming • floating • Flying – birds, bats & insects

5. Not only lectures… • Practicals - No • Group Case Study 30% • Exam • 70% paragraph answers; paper criticism

6. Case Study • group of 4 - 7 • work on problem together • submit single report • choice of 4 Studies • Group list: Wednesday 3 May 1115 • e-mail appointment; or come Wed 31 May • deadline : Friday 2 June

7. Books, etc • Purves, D (et al) (2001) Neuroscience Sinauer • Simmons PJ and Young D (1999) Nerve Cells and Animal Behaviour CUP • McNeill - Alexander R. How Animals Move [CD Rom borrow in teaching]

8. Other books on nerve • Shepherd, G. M. (1994) Neurobiology. OUP An excellent text • Nicholls, J et al (2002) From Neuron to Brain (4th ed) • Robinson, D. Neurobiology (ISBN 3-540-63778-8): (1998)

9. What needs explaining? • what are nerve cells like? • what happens at rest ? • Resting potentials • dynamic equilibrium • what happens when activated? • Action potentials • All-or-none • speed • comparative differences

10. Mammalian cells • Brain has • neurons 109 • glia 3 • 109 • blood vessels • Parts of a neuron • dendrite • soma • axon

11. Identifying cells • silver staining • fluorescent dyes • antisera

12. Invertebrate cells • Ganglion • 400 to 106 cells • nerve or neuron?

13. Summary so Far • Brains made of neurons and glia

14. Contract mantle as fast as possible Big axon (250µM) insert electrodes replace contents Squid neurobiology

15. Cells are all negative contain K+ outside Na+ anions e.g. Cl- have semi-permeable membranes Squid giant axon Resting potential

16. Bezanilla http://pb010.anes.ucla.edu/ Animations of resting potential

17. Balance between diffusion and electrical force? Use Nernst Equation to test this out Conclusion: passive balance is OK for squids Resting potential

18. Summary so Far • Brains made of neurons and glia • All cells have resting potentials • Normally maintained passively by balance of diffusion and electrical forces

19. membrane becomes permeable to Na+ Na+ floods in diffusion electrical K+ still goes out Squid giant axon Action potential

20. Action potential • Two crucial properties of the Na+ current • starts at a voltage threshold • stops itself • Arise from Na+ channel • channel is voltage sensitive and opens • closes with a second mechanism 1ms -30mV open closed inactivated -70mV

21. How do we know ? (i) • Hodgkin & Katz replaced Na+ in the seawater

22. Hodgkin & Huxley devised the voltage clamp experiment separates the ionic and capacitative currents use replace ions to determine role of each How do we know ? (ii)

23.  V  R I  Interlude • What is resistance ? • Write it down now • Rule (Ohm’s law) • V = IR • What are current and voltage? • Write it down now • Use V for voltage • use I for current

24.  V  R I  - + C Interlude • What is capacitance? • Write it down now • Resistance Rule (Ohm’s law) • V = IR • Rule • Q=CV • dQ/dt = CdV/dt • I = dQ/dt = CdV/dt

25. H&H Experiment • Step the clamp from -70mV to different voltages Voltage Current

26. H &H (ii) • Add • tetrodotoxin and block Na+ current • tetra-ethyl-ammonium and block K+ current

27. H&H reconstruction • H&H measured the kinetics of the currents • used this to postulated the kinetics of channels • used this to build a mathematical model • Animations of H&H model • Bezanilla • see http://biolpc22.york.ac.uk/632

28. Summary so Far • Brains made of neurons and glia • All cells have resting potentials • Normally maintained passively by balance of diffusion and electrical forces • Properties of Na and K channels determine action potential

29. How does it spread? • electrostatically

30. How fast is the action potential? • Up to 100m/s • major component of latency to respond • for 2m high human, 2/100*1000 = 20ms • for a 40m dinosaur... • slowed by capacitance

31. How do we know? • Myelinated axons run faster, • capacitance is reduced • channels only at Nodes of Ranvier

32. Myelination • Schwann cell (blue) grows round axon (orange) • In Multiple sclerosis (MS) myelin sheath is disrupted

33. Comparative neurobiology • Action potentials are not all the same • in vertebrates K+ current is very small • in molluscs, Ca++ current supplements the Na+ • only vertebrates have myelination, but all animals have glia • protozoa have action potentials too

34. A word of caution • students often write conductance when they mean conduction • conductance is a measure of permeability • how easy it is for ions to cross the membrane • conduction is the process of movement along the axon • e.g. conduction velocity

35. Final Summary • Brains made of neurons and glia • All cells have resting potentials • Normally maintained passively by balance of diffusion and electrical forces • Properties of Na and K channels determine action potential • Capacitance (myelination) determines speed • Web page: http://biolpc22.york.ac.uk/632/