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Mecanisme celulare i

moleculare ale excitabilitii

Excitabilitate

ExcitabilitateExcitabilitate -- ca acitateaca acitatea((condiiacondiia)) unuiunui sistemsistem viuviu dede aacaptacapta semnalesemnale specificespecifice, ca, caformformdede actualizareactualizare aa

,,organizriiorganizrii luilui ntruntruadaptabilitateadaptabilitateii continuitatecontinuitate

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Cum i de ce a evoluat viata

Care au fost alegerile/schimbrile cute?

Halobacterium salinarium

?

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Cel mai realist robot umanoid

Cercettorii japonezi au ncercat s depeascgrania dintre omi main cu ajutorul celui mairecent robot creat de ei, denumit Geminoid DK.

Acesta este cel de-al treilea robot android din seria,

la Universitatea Osaka i echipa sa de la InstitutulInternaional de Cercetare Avansat aTelecomunicaiilor din Nara.

Geminoid DK a fost construit astfel nct s semenect mai bine cu profesorul Henrik Scharfe de la

robot din aceast serie care a imitat chipul unei

persoane din afara Japoniei. Hiroshi Ishiguro anceput cu o copie a lui nsui, pe care a botezat-oGeminoid HI-1, i a continuat cu o clonautomatizat a unui manechin din Japonia, numit

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Proc Natl Acad Sci U S A. 2006 Aug 29;103(35):13080-5. Epub

2006 Au 22.

The last eukaryotic common

ancestor (LECA): acquisition of

cytoskeletal motility from

aerotolerant spirochetes in the

Proterozoic Eon.Margulis L, Chapman M, Guerrero R, Hall J.Department of Geosciences, University of Massachusetts,

Amherst, 01003, USA

Philos Trans R Soc Lond B Biol Sci. 2003

an ; : - ; scuss on - .

On the origins of cells: a hypothesis for

the evolutionary transitions from

abiotic geochemistry to

chemoautotro hic rokar otes and

from prokaryotes to nucleated cells

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Halobacterium salinarium

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On the origins of cells: a hypothesis forthe evolutionary transitions from

abiotic geochemistry to chemoauto-trophic prokaryotes, and from

Physical compartmentation from theenvironment and self-organization of self-

. .and M J. Russell, The Royal Society 2002

con a ne re ox reac ons are e mos

conserved attributes of living things, henceinorganic matter with such attributeswould be lifes most likely forebear.

The naturally arising, three-dimensional compartmentationobserved within fossilizedseepage-site metal sulphideprecipitates indicates that these

inorganic compartments werethe precursors of cell walls and

membranes found in free-livingprokaryotes.

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The known capability of FeS and NiS tocatalyse the synthesis of the acetyl-

methylsulphide from carbon monoxide andmethylsulphide, constituents ofhydrothermal fluid, indicates that pre-biotic syntheses occurred at the innersurfaces of these metal-sulphide-walledcompartments, which furthermore

into the ocean, providing sufficient

concentrations of reactants to forge thetransition from geochemistry tobiochemistry.

The archaebacterium, a thermoacidophil

A chimeric cell evolved via symbiogenesis

by syntrophic merger between anarchaebacterium and a eubacterium

,generated hydrogensulfide to protect theeubacterium, a heterotrophic swimmercomparable to Spirochaeta or Hollandinathat oxidized sulfide tosulfur.

The chimeric eukaryote: Origin of the nucleus fromthe karyomastigont in amitochondriate protistsLynn Margulis, Michael F. Dolan, and Ricardo Guerrero.

Proceedings of the National Academy of Sciences.June 20, 2000 vol. 97 no. 13

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The universal ancestor we infer wasnot a free-living cell, but rather was

confined to the naturally,

within which the synthesis of itsconstituents occurred. The firstfree-living cells are suggested tohave been eubacterial and

archaebacterial chemoautotrophsthat emerged more than 3.8 Gyr agofrom their inorganic confines.

We propose that the emergence ofthese prokaryotic lineages from

inor anic confines occurredindependently, facilitated by theindependent origins of membrane-lipid biosynthesis: isoprenoid ethermembranes in the archaebacterial

and fatty acid ester membranes inthe eubacterial lineage.

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The eukaryotes, all of which are

ancestrally heterotrophs andpossess eubacterial lipids, are

suggested to have arisen ca. 2 Gyrago through symbiosis involving anautotrophic archaebacterial hostand a heterotrophic eubacterialsym on , e common ances or o

mitochondria and hydrogenosomes

The chemistry of what is known ase -wor cou ave a en

place within these naturallyforming, catalytic walledcompartments to give rise to

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1

Cum i de ce a evoluat

Care au fost alegerile/schimbrile cute?

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How the mind came to as or we to

it is a rich and beautiful story

and, like all things biological,is still being written

Simultaneity of neuronalactivity, brought into existencenot b chance but b intrinsicoscillatory electrical activity,rezonace and coherence are atthe root o cognition. Indeed, such

ondation of the notion that thereis such a thing called ourselves

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1

Cum i de ce a evoluat

Care au fost alegerile/schimbrile cute?

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1

Mecanisme celulare i

moleculare aleexcitabilit ii celulei

nervoase

Generarea, transmiterea i

procesarea semnalului nsistemul nervos

excitabilitatePremise

permeabilitateselectiv

membranar

evoluieidentitate

Interrelaiile dintre proprietile membranei celulare i principaleledimensiuni ale existenei sistemelor biologice

adaptabilitate

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1

Molecule

hidrofobe Subst.steroidice

O2CO2N2

p

Glicerol

Uree

ZaharozGlucoz

micinepolare

Moleculemarinepolare

Na+, H+, K+

Ca2+, Mg2+

HCO3-, Cl-

Ioni

Interaciuneastimul - receptor - rspuns

r r

chimic

fizic

stimulcepto

oceso

rspuns

RePr

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1

La nivelul cel mai elementar, noi

sarcinelectric...

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1

Extracelular

Bistrat

lipidic

(3nm)

Retinal

legat de

lizina

Bacteriorodopsina (Alberts

B. 2008)

Citosol

transport membranar

canal

bistrat

lipidic

pro e c ranspor or

Gradient de

concentraie

transport pasiv

difuzie

simplamediatde canale

mediatdetransportori

mediatde pompe

transport activ

adaptat dupMOLECULAR BIOLOGY OF THE CELL. 2008

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2

-

Canale ionice

termenul i a inregistrat curentul deleziune

Emil du Bois-Re mond 18181896 esutul viu este compus din molecule

electrice

Sidney Ringer (18361910) Rolul Ca ncontracia muscular

Canale ionice

n 1902 Julius Bernstein 1839-1917- celula excitabileste mrginitde omembranselectiv permeabil pentruK n repaus i devine permeabilpentru ali ioni n timpul excitrii

In 1907, John Newton Langley (18521925) a introdus conceptul demoleculreceptor pe suprfaa celulelornervoase i musculare

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2

Canale ionice

Definiie - structuri proteice transmembra-nare, celulare sau subcelulare ce permit

transportul ionic conform gradientului

electrochimic

Clasificare - f(x) mec. de funcionare:

(pasiv)

-canale ionice controlate (gated)

- ,

(nongated)

Structura-proteine coninnd pnla 2000

aa, organizate n 3-6 segmente

Canale ionice

transmembranare; peste 400 de gene

controleazformarea canalelor ionice

170 gene pt. canalele de K, 38 pt Ca, 29 pt

, , .glutamatergici

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2

Canale de Na+ voltaj- dependente

identificat 1970

Structura canal de Na voltaj dependent

PP

Canale ionice frpoart(de repaus)

-asigurmeninerea potenialului de

Clasificare: K+, Na+, Ca2+, Cl-

repaus prin transportul ionic pasiv, nechilibru cu transportul activ primari secundar

- .redus dect cel prin canale ionicecontrolate (cu poart)

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2

Canale ionice

Canale ionice controlate (gated)

-

- controlate (gated) de mediator

- controlate ated mecanic

Canale ionice cu poartParticulariti:

- ...

-participla generarea, transmiterea sau

modularea potenialului de aciune

-au fost descoperite primele-prez n o vers a e ma mare

-reprezintprincipala int

tera eutic

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2

Canale ionice cu poart

o a epen en e

Canale de Na

+

voltaj- dependenteidentificat 1970

Structura canal de Na voltaj dependent

PP

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2

-subunitatea - (1-9/ Nav 1- 9)

Canale de Na+ voltaj- dependente

- -

-subunitatea

-formeazporul canalului

-

- ancoreazcanalul nmembrana celular

Distribuie, rolCanale de Na

+

voltaj- dependente

Nav 1-3, Nav 6-9 n SNP, SNC cu

rol in durere pot fi mai multe

tipuri pe acceai celulnervoas

Nav 4-5 n m. scheletic i miocard

Nav1.6 n celule imune, microgliai macrofage

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2

extracelular

Canale de Na+ voltaj- dependente

membrancelular

+

poartdeinactivare

poartdeactivare

REPAUS (nchis)

ACTIVAT (deschis)

+

+

INACTIVAT (nchis)

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2

Canale ionice Ach

Schema generala a receptorului de NMDA

NMDA N-metil-D-aspartat; PCP- fenciclidina; MK-

801 - dizocilpina

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2

ainat

ainat

0000nM

,CA3

nM

,CA3

KK 22

icuculin

icuculin

00M,

CA3

M,

CA3

CONTROLCONTROL CRICRIZEVOCAT CRIZSPONTANZEVOCAT CRIZSPONTAN

Bicuculina

Canale ionice cu poart

on ro a e mecan c

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3

intracelular

situs de

ancorare

STIM

extrcelular

membrancelular

protein

fibrilar

membran

celular

intracelular

situs de

ancorareextrcelular

STIM

membran

celular

poartprotein

fibrilar

intracelular

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3

particulariti funcionale

POMPE IONICE

- ranspor ac v- on , mo . organ ce

- implicreacii enzimatice

- ratmicde transport

POMPE IONICEtip P

- ompa a-

- Schatzmann 1953 glicozide cardiace

- Skou, 1957 ATP-aza activata de Na i K

1977, PN

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3

citosol

extracelular

ROL

EEExxxtttrrraaaccceeelllAAA

Pompa de Ca

+++

IIInnntttrrraaaccceeelll...

NNN

CCC

uuusss eee eeegggaaarrreee aaa aaa

SSSiiitttuuusssuuulllAAATTTPPP---aaazzzeeeiii

CCCaaalllmmmoooddduuullliiinnn

SSSiiitttuuusssuuullldddeeellleeegggaaarrreeeaaaAAATTTPPP

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3

Transportori ionici

- Na/Ca

- Na/H

- Cl/HCO -

- Na/ aa, Na/G

- Na/HCO3

- Na/K/2Cl

- K/Cl

3Na+

K+

H+

H+

Ca2+

POMPE

K+

TRANSPORTORI

Cl-

Ca2+

K+

Cl-

Cl-

AA

Na+

CANALE

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3

Transport ionic membranar

Interrelaii excitabilitate-

Concluzii

metabolism

Transm terea procesarea

semnalului n sistemul nervos

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3

Distribuia sarcinilor electrice

Concentraia intra- extracelularaprincipalilor ioni n celula mamiferelor

Ion Extracelular IntracelularNa+ 145 12K+ 4 155

2+

. . . .Cl 123 4.2Mg2+ 1.5 0.8

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teaca demielin

nod Ranvier

strat demielin

strat demielin

nucleu