Clinical Neurophysiology

Transcription

1 Clinical Neurophysiology 2013 Dept. of Neurology

2 Basic and clinical Neurophysiology Basic neurophysiology Identify mechanisms that make the nervous system work Molecules, cells, groups of cells, functional systems Invasive, time consuming, small number of subjects studied Clinical neurophysiology Diagnose disease in patients Correlates of functions of the intact human body Reliable, fast, cheap, benefit justifies the risk

3 focus of neurophysiology molecules cells systems

4 parts of a nerve cell dendrites summation of input cell body metabolism axon propagation of the signal synapse transmission of the signal

5 functions in nerve cells chemical electrical reception of information calculation signal transport signal transmission

6 biological membranes lipid bilayer (glycerole ester) electrical isolation chemical isolation membrane proteine signal transduction mechanical stablility immune mechanisms transport

7 electrical phenomena in nerve cells 1st step: resting state of a membrane patch: Why do nerve cells have a resting potential? 2nd step: action potential of a membrane patch: Why can nerve cells change their electrical properties? 3rd step: propagation of the action potential: Why does the action potential propagate along an axon?

8 excitable membranes: resting potential starting situation concentration difference between intracellular und extracellular conduction across membrane only for kations chemical gradient

9 excitable membranes: resting potential inside outside chemical gradient

10 excitable membranes: resting potential equilibrium: zero current positive charges on the outside V Na RT zf ln c c IZR EZR chemical gradient electrical gradient (Nernst potential)

11 excitable membranes: resting potential chemical gradient starting situation concentration difference for two varieties of kations different conductivities for kations chemical gradient

12 excitable membranes: resting potential chemical gradient (ouside) (inside) chemical gradient

13 excitable membranes: resting potential chemical gradient electrical gradient equilibrium more diffusion of the ions with larger conductivity outside charged positively equal currents by both kations potential across the membrane depends on conductivities chemical gradient electrical gradient

14 Excitable membranes as a weapon Electrophorus electricus Electrical organs with electroplaques (adapted from muscle cells) 500 V, 2 A by using membrane potentials in a serial circuit

15 excitable membranes: resting potential chemical gradient electrical gradient equilibrium flux blue in balances red out in the long run breakdown of concentration differences chemical gradient electrical gradient

16 excitable membranes: resting potential chemical gradient electrical gradient equilibrium flux blue in balances red out in the long run breakdown of concentration differences chemical gradient electrical gradient

17 electrical phenomena in nerve cells 1st step: resting state of a membrane patch: Why do nerve cells have a resting potential? 2nd step: action potential of a membrane patch: Why can nerve cells change their electrical properties? 3rd step: propagation of the action potential: Why does the action potential propagate along an axon?

18 excitable membranes: action potential i action potential depolarisation hyperpolarisation

19 excitable membranes: action potential starting situation: K conductivity and Na conductivity small (K + >Na + )

20 excitable membranes: action potential 1st step in the action potential: increase in Na conductivity reversal in the membrane potential: depolarisation

21 excitable membranes: action potential 2nd step in the action potential: increase in the K conductivity membrane potential returns to baseline: repolarisation

22 excitable membranes: action potential 3rd step in the action potential: Na channels inactivated membrane potential below resting potential: hyperpolarisation

23 excitable membranes: voltage gated sodium channels 3 states: open closed inactivated open inactivated transition between states with votage dependent rates closed

24 excitable membranes: voltage gated sodium channels resting potential depolarized open inactivated open inactivated transition to triggers chain reaction closed closed

25 excitable membranes: voltage gated sodium channels state of channels influences membrane potential membrane potential influences state of channel

26 excitable membranes: action potential Trigger for the action potential: abrupt opening of sodium channels

27 Simplified version of the Hodgkin-Huxley equations C dr dt dv dt R g 1 Na V RV E g R V E g V E I M V R G V Na K K leak leak M R V G V V V 45 V 70 ; 0.1 ; 4exp V exp exp V S N S 1 H ; S S 2 N V H V V 60 V 70 ; ; 0.125exp V exp 1 10 V 70 1 ; 0.07 exp ; 20 V 40 exp 1 10 RINZEL J (1985) EXCITATION DYNAMICS - INSIGHTS FROM SIMPLIFIED MEMBRANE MODELS. FEDERATION PROCEEDINGS 44:

28 Phase plot of Rinzel system Schwelle: I = µa I = 10 µa RINZEL J (1985) EXCITATION DYNAMICS - INSIGHTS FROM SIMPLIFIED MEMBRANE MODELS. FEDERATION PROCEEDINGS 44:

29 excitable membranes: voltage gated sodium channels Tetrodotoxin: blocks sodium channels high concentration in Fugu

30 electrical phenomena in nerve cells 1st step: resting state of a membrane patch: Why do nerve cells have a resting potential? 2nd step: action potential of a membrane patch: Why can nerve cells change their electrical properties? 3rd step: propagation of the action potential: Why does the action potential propagate along an axon?

31 propagation of the action potential Depolarized membrane patch axon

32 propagation of the action potential depolarisation to threshold Sodium channels inactivated axon

33 propagation of the action potential Axon axon Concentration of the current at Ranvier nodes axon

34 Fortgeleitetes Aktionspotential Intracellular recording Surface recording

35 sensory neurography

36 sensory neurography Latenz: 2.8 ms; d=14 cm NLG =?

37 Suggested reading Wilson HR (1999) Spikes, Decisions and Actions. Dynamical Foundations of Neuroscience. Oxford, 1999