COGNITIVE SCIENCE 107A

Transcription

1 COGNITIVE SCIENCE 107A Electrophysiology: Electrotonic Properties 2 Jaime A. Pineda, Ph.D.

2 The Model Neuron Lab Your PC/CSB115 Labs - Electrophysiology Home - ModelNeuron.zip Download ModelNeuron.zip Uncompress ModelNeuron.zip Double click on ccwin32 Do the assignment. *** PASSIVE.CCS=PASS.CCS, ACTIVE.CCS=ACTIV.CCS

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4 Modern Electrophysiology Many ion channels differ in: Trigger (ligand, voltage, stretch) Time course (transient/sustained) Sensitivity to V m and ligands (low/high threshold/affinity) Ion channel distribution varies across neuron Nonuniform but not random distribution Highest Na+ channel density in IS Ion channels change frequently up/down regulation

5 Differences in Channel Currents I Nat rapidly activating/inactivating Na current I Nap persistent Na current, which does not inactivate; activated by subthreshold inputs; controls responsiveness of cell; responsible for plateau potentials - related to memory processes?

6 Differences in Channel Kinetics K channel Ligand- and voltagesensitive gate Opens by depolarization of Vm (activates) Closes by repolarization of Vm (deactivates) Na channel Ligand and voltagesensitive gate Activates Deactivates Inactivates (despite depolarization) Deinactivates (removal of inactivation)

7 Ion Flow During an Action Potential

8 Na+ / K+ Pump (Transmembrane ATPase an enzyme that catalyzes ATP into ADP and releases energy) Restores equilibrium

9 Na + -K + -ATPase The pump, with bound ATP, binds 3 intracellular Na+ ions. ATP is hydrolyzed, leading to phosphorylation of the pump and subsequent release of ADP. A conformational change in the pump exposes the Na+ ions to the outside. The phosphorylated form of the pump has a low affinity for Na+ ions, so they are released. The pump binds 2 extracellular K+ ions. This causes the dephosphorylation of the pump, reverting it to its previous conformational state, transporting the K+ ions into the cell. The dephosphorylated form of the pump has a higher affinity for Na+ ions than K+ ions, so the two bound K+ ions are released. ATP binds, and the process starts again.

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11 Advantages of myelination Reduces number of ion channels Reduces number of Na+ / K+ pump Increases speed of conduction Reduces energy needs

12 Saltatory Conduction

13 Characteristic Patterns of Activity Regular firing One spike at a time Intensity of stimulation increases rate Rhythmic bursts Regular/irregular Spike frequency adaptation Slow oscillatory

14 NERNST EQUATION (Walter Nernst, 1888) A way to determine the equilibrium potential for a specific ion assumes no pump E Na+ = +56 mv E Cl- = - 60 mv E K+ = - 75 mv E Ca++ = +125mV At body temperature (37 o C): E = 61.5 x log 10 [ion] o /[ion] i Rule: The membrane potential of a cell will be closest to the equilibrium potential of the ion to which the membrane is most permeable.

15 Membrane Potential: Goldman-Hodgkin-Katz Equation P = permeability (pk:pna:pcl = 1:0.04:0.45) Net potential movement for all ions known V m :Can predict direction of movement of any ion ~

16 biological realism

17 Compartment Models Neuron can be modeled as an electrical circuit with some simplifying assumptions: Segments are cylinders with a constant radius Current in a segment flows like in a cable

18 Other Assumptions The lipid bilayer is represented as a capacitance (C m ) Ion channels are represented by resistors or electrical conductances (g n ) The electrochemical gradients are represented by batteries Ion pumps are represented by current sources (I p )

19 Electrochemical gradients resemble a battery OUTSIDE POS INSIDE NEG

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21 Electric current flows in accord with the following equations: V = I x R (Ohm s Law) V = V m E r V = electrotonic potential V m = changed membrane potential E r = resting membrane potential Thus, one can construct an equivalent circuit per segment C m - capacitor E m - battery R m - membrane resistance R a - axial resistance G m - conductance reciprocal of resistance I - current source

22 Compartment Models (assumptions cont.) Electrotonic current is Ohmic in accord with the equation: V = I x R (Ohm s Law) Current divides into two local resistance paths: internal or axial (r i or r a ) current membrane (r m ) current Axial current is inversely proportional to diameter r i = Ri/A where A = πr 2 Membrane current is inversely proportional to membrane surface area (and density of channels) r m = R m /c where c=2πr

23 Steady-state solution in centimeters

24 r m = R m /c r i = R i /A

25 SPATIAL SUMMATION

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27 Transient-state solution (the importance of membrane capacitance - Cm) Capacitance how rapidly a membrane charges up (low pass filter)

28 TEMPORAL SUMMATION

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30 Velocity of electrotonic spread is equal to 2 * (lambda/tau) Synaptic integration is non-linear

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32 Variables that contribute to integration Cellular properties Space/time constants Membrane potential Thresholds Spike frequency adaptation Delayed excitation Synaptic properties Sign (+/-) Strength Time course Type of transmission Chemical Electrical

33 TTX (tetrodotoxin) And TEA (tetraethyl ammonium) block I Na and I K, respectively Pyramidal cells -75mV Thalamic cells. -65mV Photoreceptors -40mV

34 Phases of the Action Potential Absolute refractory period Relative refractory period Firing threshold is the point at which the number of activated Na+ channels > inactivated Na+ channels

35 Determining Rate of Firing Absolute refractory period mediated by the inactivation of Na + channels. Relative refractory period occurs in the hyperpolarization phase.