Kategorie: Wszystkie - dynamics - stability

przez Fatima Sharif 3 lat temu

278

mod 3

mod 3

dv/dt = Iapp (t) - Iion (V) Iapp (t) = C dv/dt + Iion (V)

Imem = Cdv/dt + Iion (V)

Imem= Icap + Iion

Floating topic

inward / outward

hyperpolarization (+ -V) ion (+ +V)

restorative (+slope) regenerative (- slope)

restirative
regenerative
negative conduction

Cellular biophysics and modeling

ODE Modeling

bifurcation
phase plane analysis
phase diagrams
^ f(x) on y and state variable x on x axis (derivative as a function of underived function)

idenitfy critical points, cross at x axis is css

d/dx {f(xss)} = 0 (y axis)

determine stability by lookin at a fllow directions

preturb off its xss: n = x -x*

dn/dt= d/dt (x-x*)= f(x) - f(x*)

= f(x) = f(x* + n)

= 0 + nf' (x*) + 0

< 0 stable

speeding toward

> 0 unstable

speeding away

derivative of f(x*) is not 0 bc this is f''

via expansion taylor dn/dy = f(x*) + nf'(x*) + O(n²)

very small perturbation so third term is negligible

dn/dt = f(x) - 0

Experimental Recording Methods

voltage clamp recoding FIXED VOLTAGE, MEASURE CURRENT
applied current adjusted so that V = Vcommand

Depolarizing or depolarizing voltage


Change I app very fast


to create steps (pulses)


instantanous

dv/dt = 0 0 = Iapp - I mem (C +) I mem = Iapp

What happend to C ?????

(Depolarizaing) Pulses

steps to higher voltages)

1 - Measure

2 - Compare

3- Correct

4 - Inject

5 - Monitor

changing salt concentrations

axons dont have other than Na + an k+ channels

current clamp recording

Membrane potential dynamics

capaticence = ability to store and separate charge = lipid bilayer because they are impermeatble

Current (C/t) = A

kirchoffs current law =I res + I cap - I app = 0

current balance equation

C(dV/dt) = Iapp - Imem

Imem = Σion

Ileak + Ina + Ikv Hogdkin-Huxley

Ileak +Ica (Bistable)

Ileak Passive cell

Iion= gk(Vm-Ek)

exponential relaxtation

dv/dt= [(Iapp +gkEk)/C] - (gk/C) V phase diagram

Vss = (Iapp/gk)+ Ek

J/K
or from equation
when f(0) ; 0 = Iapp - gk(Vss - Ek)

-Iapp, left shift

+Iapp, right shift

When Iapp = 0 , resting potential

slope = gk/C

exponential time contant = C/gk

Iapp

+ / OUTWARD

+ ions in --> out

Na + or Ca2+ leaving

- ion out --> in

ex GABA cl- outward currnets


Cl- entering

- / INWARD

hyperpolarizing

applied current

depolarizing

- in --> out

Cl- moving out the cell
doesn't happen?

+ ions out --> in

Na+ or Ca++ entering

current voltage relations

Ires

Vm = Ek + Vres =φin - φ* + φ* - φout

Vm = Ek+ Ires / gk

Ik = gk(Vm-Ek) chord conductance equation form

current over resistor (ion channel)

when Ik is - , Vm is less than Equilibrium

when Ik is + , Vm is greater than Equilibrium

K+ driving out of cell

Ek = φin -φ*

special case of ghk current equation



GK -- current ---> voltage ---> nernst

Vres

φ* - φout

Ires/ gk

IresR

R=1/gk

I cap

for every one charge that enters, one leaves from other side through nothing actually really passes

Icap = dQ/dt = C (dVm/dt)

Q = CVm

C = capacitance

transmenbrane potential

constant field theory

ions move single file through the membrane

ions in membrane behave like ions in a solution

obey nerst-planck equation

voltage changes linearly through membrane

electric field is constant

Vm = φin - φout

as +ions that are higher [outside] are allowed in move in, will do so nonlinearly because gradually will want to move in less because electromotive force that is opposing the still existing concentration graduient

Goldman hodkin katz (ghk) voltage equatoion

note that cl has flip i/o so that we don't need to use z


+1 * +1 = -1 ^ 2


1*2 = -1^2

α = PNa/PK

how close Vm will be to nerst depending on [K+]

K+ dominates resting potential

only revelent when [K+] is low

a<<<1 and so [Na]i<<<[K]i therfore

assume Pcl<<< PK (we did same for Ca++)

nernst EQUILIBRIUM potential

finding when electromotive force and concentration graduant force are equal opposing

E force - C force = 0

RT(ln[Kin]/[Kout])/zF

no net current

V= φin - φout = Ek

GHK current density equation

predicts non lineariity bc mutiple variables inviolved

ions move because diffsion and drift (C and electromotove)

[S]out

[S]i

Ps

zF

zV/Vθ

vθ = RT/F

opposite for K+ and flip out and in anions

inwardly rectifying K+ potassium current

shifts

toward depolarization with equal but opposite Iapplied is smaller than toward hypoerpolarizatneasier to flow inward

for Na+

ratio defines amount of retification

reversal potential = nernst potential where current reverses

outward (convex), small g, + current

as V--> -inf, denom --> inf // I Na --> 0

as V --> inf, denom --> 1 /// I Na prop to [Na+]i

inward reticification (concave), g large, current flows easy when inward (-, <0)

as V --> -inf, num --> denom // I Na prop to [Na+]0

as V --> inf, num --> 0 // I na+ therefore --> 0

ion Channels

Na+ and ca2+ channels

4 * 6tmd (1p), basically 4 of ^ connected

K+ channels

closed at rest

6tmd, 1p, 4x

***** 4rth tmd has + reasons that allow voltage dep gating

TRP

KCNQ

Kca ca2+activated

Kv voltage dep

Open at rest therefore determine most of resting

4 tmd 1p, 2x

k2p channels

2tmd 1p, 4x

KcsA

picture is half
showing xx // xx

Kir inward-reticfying

extensive vs intensive

extenstive

x^2
when x*2
factor by 4

membrane capacitance

membrane resistance Rm = Rm/ SA

4πr^2

intensive

capacitance

memebrane reistivity Rm = 10000 Ωc^2

conductance is nonnegative NOT CURRENT



n gates


4 gates


so the moventnt of any one 4 gates has ability to move close gate since 4 particles must be in a particular configuration

n∞

IK+ activation and decativation

h∞

I na inactivation

inactivation - activating stimulus maintained but conductance went away

when you try to evoke Na current again there is a refractory period u can evoke same activation. time constant has to do with recovery timee fold of its final value

Na+ inactivated but K+ activated

m∞

voltage dependant rate constant

gating variable (m)

(bc channels have voltage dependant gates)


which also is why they inactivate after same evokedvoltage too

order of magitigude (10x) faster, react to changes

dm/dt = α(1-m) - βm

= α-m(α+β)

dx/dt = a + bx

antiderivative

τ = 1/ b

xss = a/b

dc/dt = j - kc

Cdv/dt = I app - gk ( V - Ek)

How close is M to its steady state value? How fast is scaled by time constast (big-slow vv)

Tau

M ss

(1-m) ⇌ m

m[0,1]

β : open --> closed

α: closed --> open

deactivation- falls back to 0 state bc evoked stimulus is removed

Na+ activation

Action potentials (excitability)
Hodkin huxley discovered there 2 currnets in action potentials

separation and subtraction of ionic currents

LAST THREE MINUTES OF 9.1????????????
embracing currents can be isolated via ion subsists ion and digital subtraction

transient (happens when inactivate)

capacitive transient

I ion - Activation of K+ current when voltage back -10 --> -70, low driving force because ion channels decativate

only flows at instant voltage changes

I T

restorative e

regernative regernative

mathematically stable unrealistic because system cant maintain like a pen standing upright

restoraive restorative

equal and opposite so cancel out

3 points at which intersect

state stapcs vs parameter (Iapp)= bifurfaction diagram

hyteresis

shifting Iapp can chahnge stabilities

membrane bistability

stable at 2 different Vs and a transient current can switch you between the two

currents on either eside of the 2 steady states are resorative (positive conductance) an perturbation would restore to Ek. membrane would fall back down unless you reach threshold

3 times interescts x axis, current is 0

perisistent

delayed-reticifier

I potassium - DR = conductance m^n (Driving force)

opposite shape for hyperpolarization

activation by hyperpolarization

Ih or Isag

inward recitfying potassium current Kir

always open until threshold or

actiavtion by depolarization

I CaV depolarization activated Ca2+ current

V dep current

basically same as conductance equation with the factor of driving force

V dep conductance

I Kv

once reaches m inf all conduxctance is available (all channels open)

physiological range

Subtopic

slope g / E is equilib / current is dep on driving force (E--> eq disparity / once cross x, start leaving cell vs entering / there's a curve when whntering is highly pref

move up and squash

THRESHOLD is AP THRESHOLD

ALL OR NONE

point of highest slope

determines whether channels are open or closed (max vs min conductance

conductance as a function of voltage

peaks at Na becomes given a voltage and also where I will eventually steady given voltage

K+ , delayed outward current

Na+, early inward current

changing Na concent only saw change in the early inward curent

the 2 blips at +70 and +90 mv are evoke at volatges above nerst potential

Main topic