The proper starting point is to ask whatfiziologie.ro/didactic/2019-2020/cursuri/NFZ C 1... ·...
Transcript of The proper starting point is to ask whatfiziologie.ro/didactic/2019-2020/cursuri/NFZ C 1... ·...
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The proper starting point is to ask what students should know and be able to do as a
result of their education.
Human achievement in every field is driven by the desire to explore, to test and prod, to see what happens, to question how things work, and to wonder why and ask, what if?
Ken Robertson and Lou Aronica. Creative Schools. Viking Penguin. 2015
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For some of us, curiosity about some things may be short-lived and quickly satisfied. For others, it may become a sustaining passion on which whole lives and careers are spent. In any case, a lifelong sense of curiosity is one of the greatest gifts that schools can give their students.
Ken Robertson and Lou Aronica. Creative Schools. Viking Penguin. 2015
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It is not enough to teach man a specialty. Through it he may become a kind of useful machine but not a harmoniously developed personality. It is essential that the student acquire an understanding of and a lively feeling for values... Otherwise he-with his specialized knowledge-more closely resembles a well-trained dog than a harmoniously developed person.
A.Einstein. Ideas and Opinions. Crown Publishers, 1954.
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Cogito, ergo sumDubito, ergo cogito
R.Descartes – Discurs despre metodă. 1637
Sum, ergo creo
Mă îndoiesc, deci gândesc Gândesc, deci exist Exist, deci creez
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…din gândirea unui analfabet funcțional cu licență în medicină. Extras din lucrarea pentru examen admitere doctorat. 2014
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Norme de parteneriat
participare la curs; cursul=creație
pregătire pentru curs
dialog cu profesorul
verificare cunoștiințe, seminarii-ex.
studenți buni
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Neurofiziologie -curs
Transmiterea şi procesarea semnalului în sistemul nervos
Fiziologia senzorială
Mecanisme neurobiologice ale excitabilității
Integrarea funcțiilor cerebrale
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Noţiuni introductive
Organizarea morfofuncţională a sistemului nervos
Macroscopică
Microscopică
Funcţională
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Organizare morfofuncţională a SNMacroscopică
-sistem nervos central
-sistem nervos periferic
Microscopică
-celule: neuroni
-celule: celule gliale sinapse
Somatic Vegetativ(autonom)
-teoria neuronală – H. von Waldeyer.1891
-bariera hemato-encefalică
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Aspectul macroscopic
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H Berger - de la telepatie la EEG -1926
Suport electric- L Galvani 1791
Aristotel 384-322 î.c.- inima sediul mişcării si vieţii psihice. T.inexcitabilităţii cerebrale 1870
Medicul regelui Filip cel frumos după 1300 scrie: “creierul este... rece şi umed pt. a diminua extrema căldură şi uscăciune a inimii, alb pt. a fi ca o tabula rasa şi a primi orice imagine, lax şi moderat de vâscos pt. ca lucrurile percepute să-l străbată uşor...
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The brain is a kludge. David J. Linden
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But nanobot-mediated virtual reality is only the beginning. Kurzweil predicts that by the late 2030s, we will be able to routinely scan an individual’s brain with such molecular precision and with such a complete understanding of the rules underlying neuronal function and plasticity that we will be able to “upload” his mental processes into a vastly powerful and capacious future computer. As Kurzweil describes it, “This process would capture a person’s entire personality, memory, skills and history.
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A more controversial application than the scanning-the-brain-to-understand-it scenario is scanning the brain to upload it. Uploading a human brain means scanning all of its salient details and then reinstantiating those details into a suitably powerful computational substrate. This process would capture aperson's entire personality, memory, skills, and history.
Ray Kurzweil. The Singularity Is Near. Viking Penguin.2005
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Boron pag. 276
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Gigandet X, et al. Estimating the Confidence Level of White Matter Connections Obtained with MRI Tractography. PLoS ONE 3(12): . (2008)
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Essayed I. Walid. White matter tractography for neurosurgical
planning: A topography-based review of the current state of the art.
NeuroImage: Clinical 15 (2017) 659–672
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Lungimea totală a capilarelor cerebrale- 400 mile
Distanța neuron-capilar - 20 µm
Circulația cerebrală -bariera hemato-encefalică
- bariera hemato lichidiană
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Organizare morfofuncţională a SN
-14.000 gene exprimate în dezvoltarea și funcționarea creierului
-Genomul uman- cca. 22.000 gene
Suportul genetic al SN
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This neuroepigenetic view suggests that DNA, RNA and protein each influence one another to produce a holisticcellular state that contributes to the formation and maintenance of memory, and predicts a parallel and distributed system for the consolidation, storage and retrieval of the engram.
Marshall P. Bredy T W. Cognitive neuroepigenetics: the next evolution in our understanding of the molecular mechanisms underlying learning and memory?. NPJ Sci Learn. 2016.
Organizarea funcţională a SN
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Boron pag. 283
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Boron pag. 285
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Funcții principale ale neuronului
-metabolism energetic
-sinteza moleculară
-transport-anterograd -retrograd
-generarea și conducerea potențialului de acțiune
Boron pag.256
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Boron pag.260
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Boron pag.260
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Boron pag.260
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Boron pag.258
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Mecanisme celulare şi
moleculare ale
excitabilităţii
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Excitabilitate - capacitatea
(condiţia) unui sistem viu de a
capta semnale specifice, ca formă
de actualizare a informaţiei,
necesară organizării lui întru
adaptabilitate şi continuitate.
Excitabilitate- noțiuni generale
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Câmpul electromagnetic este realitatea fizică cu care suntem în contact permanent şi nemijlocit, deşi nu avem simţuri pentru a o percepe. În odaia în care stăm, în parcurile în care ne plimbăm, în noi înşine, totul este plin de câmp electromagnetic, în fiecare moment, datorită câmpului electromagnetic, fiecare cută a fiinţei noastre este pătrunsă de toate melodiile care se cântă pe Pământ, ba şi de şoapte din afara lui, rostite poate cu miliarde de ani în urmă. A.Ţugulea- Câmpul electromagnetic? Ed. Agir, 2011
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Nicole Kelly was born without her lower right arm, but using a cutting-edge prosthesis she got last year, she can now grind pepper, play cards, and open beers — just by thinking about the action.
...Johns Hopkins Univ. bioengineering lab that is developing a glove that can feel pain just like a real hand.
https://futurism.com/the-byte/prostheses-arm-nerves.
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La nivelul cel mai
elementar, noi nu
suntem o reacţie
chimică ci o sarcină electrică...
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In timp ce curentul electric într-un fir metalic este generat de prin fluxul de electroni, curenții electrici membranari sunt generaţi de ionii anorganici
principali ai lichidelor biologice: Ca2+, Na+, K+, Cl− și HCO3−.La nivel molecular, curentul electric care traversează membrana celulară se propagă prin: canale ionice, transportori ionici electrogenici
•și pompe ionice electrogenice.
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Interacţiunea stimul - receptor - răspuns
chimic
fizic
stimul
R e
c e
p t
o r
P r
o c
e s
o r
?răspuns
?-ritmicitate, activitate neuronală spontană (ANS)
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Molecule
hidrofobe Subst.
steroidice
O2
CO2N2
Apă
Glicerol
Uree
ZaharozăGlucoză
Na+, H+, K+
Ca2+, Mg2+
HCO3-, Cl-
Molecule
mici
nepolare
Molecule
mari
nepolare
Ioni
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Boron pag.103
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-osmolalitate -electroneutralitate
-transport cuplat/necuplat-gradient electrochimic
-volum celular -EXCITABILITATE Er. 105
Boron pag.104
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Boron pag.106
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Sistem de transport ionic membranar
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transp. pasiv
transport membranar
difuzie
simpla
mediată
de canalemediată de
transportori
mediată de
pompe
transport activ
bistrat
lipidic
canal
proteic transportori
Gradient de
concentraţie
adaptat după MOLECULAR BIOLOGY OF THE CELL. 2008
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Boron pag.109
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Boron pag.109
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Canale de Na+ voltaj- dependente
Structura canal de Na voltaj dependent
identificat 1970
PP
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Curent de poarta
_ _ SCTXTTX
+ +
+ +
+ +
+
+ +
+ +
+ +
+
__ __
LA
Senzor de voltaj
Bis
trat
lip
idic
BTX
Poarta
Po
r
Extracelular_ _ SCTXSCTXTTXTTX
+ +
+ +
+ +
++
+ +
++
+ +
+ +
+ +
+ +
+
__ __
LALA
Senzor de voltaj
Bis
trat
lip
idic
BTXBTX
Poarta
Po
r
Extracelular
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poartă de
inactivare
poartă de
activare
extracelular
membrană
celulară+
Canale de Na+ voltaj- dependente
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REPAUS (închis)
+
INACTIVAT (închis)
ACTIVAT (deschis)
+
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Saxitoxină
Novocaina
TEA
TTX
Variaţia PA indusă de blocanti (agenți farmacologici). PA de control (linie
continuă) este modificat prin administrarea de agenți farmacalogici (tetrodoxină,
novocaină și saxitoxină pentru canalele de Na voltaj-dependente și
tetraetilamoniu pentru canalele de K voltaj-dependente) linia discontinuă. Se
constată modificări ale amplitudinii sau duratei PA, cu efecte asupra
excitabilității.
Mordecai P. Blaustein. Cell. Physiol.and Neurophysio. Ed. Elsevier 2012
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Tipuri de receptori /canale ionice
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Schema generala a receptorului de NMDA
N-metil-D-aspartat; PCP- fenciclidina; MK-801 - dizocilpina
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Ka
ina
t
20
0 n
M,
CA
3
CONTROL CRIZĂ CRIZĂ EVOCATĂ SPONTANĂ
Bic
ucu
lin
ă
20
M
, C
A3
B
A
Echilibrul excitatie inhibitie/relația agonist-antagonist
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Legenda pt. relația agonist-antagonist
A. Administrarea de Kainat (agonist glutamat-
ergic) induce după cca. 10 min activitate
electrică epileptiformă (aee), inițial, după
stimulare electrică, ulterior, în mod spontan.
B. Administrarea de Bicuculină (antagonist
GABAergic), induce după cca. 10 min activitate
electrică epileptiformă (aee), inițial, după
stimulare electrică, ulterior, în mod spontan.
Inregistrările aee au fost realizate pe secțiuni de
creier animal, perfuzate cu lichid cefalorahidian
artificial, in care au fost administrate kainat și
bicuculină.
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membrană
celulară
poartăproteină
fibrilară
situs de
ancorareextrcelular
intracelular
Când celula este alungită, proteina fibrilară
fixată pe situsul de ancorare deschide
poarta canalelor ionice
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membrană
celulară
extrcelular
intracelular
membrană celulară
intracelularsitus de ancorare
proteină fibrilară
Când distanța dintre două celule învecinate
crește, proteina fibrilară fixată pe situsul de
ancorare dintr-o celulă, deschide poarta
canalelor ionice din celula învecinată
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Canale voltaj-dependente- Canale pentru Na+
- distribuţie – 30-10000/µm²- 10 gene pt. Na V
-subunitatea α - (α1- α9/ Nav 1- 9)
-subunitatea β
-1800-2000 aa- formează porul canalului
- controlează transportul ionic- ancorează canalul în membrana
celulară
- structură
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Like Sisyphus, ATPase pumps are condemned to push Ca2+ uphill for eternity into the endoplasmic reticulum (ER) (via sarcoendoplasmic reticular Ca2+ ATPases; SERCA pumps) or out of the cell (via plasma membrane Ca2+ ATPases; PMCA pumps) Clapham DE.Calcium Signaling. Cell. 2007. Dec 14;131(6):1047-58.
Pompa de CalciuCalcium ions (Ca2+) impact nearly every aspect of cellular life. ... changes in protein conformations Ca2+-mediated signal transduction and its specific roles in excitability, exocytosis, motility, apoptosis, and transcription. ...Calcium ions and phosphate ions have come to rule cell signaling.
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Maintaining and Using Ca2+ Gradients for Signaling.
The cytoplasmic Ca2+ level is low in resting cells.Clapham DE.Calcium Signaling. Cell. 2007. Dec 14;131(6):1047-58.
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Maintaining and Using Ca2+ Gradients for Signaling. The cytoplasmic Ca2+ level is low in resting cells. Cytoplasmic [Ca2+] is maintained at ~100 nM by extrusion via plasma membrane Ca2+ ATPase(PMCA) and smooth endoplasmic reticular Ca2+ ATPase (SERCA) pumps (transporters)
Clapham DE.Calcium Signaling. Cell. 2007. Dec 14;131(6):1047-58.
The Na/Ca exchanger (NCX), a major secondary regulator of [Ca2+],is electrogenic, exchanging three Na ions for one Ca2+. Intracellular Ca2+ hyperpolarizes many cells by activating K+ channels, and in some cells, Cl−
channels. This decreases CaV channel activity but increases the driving force across active Ca2+ -permeant channels
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Maintaining and Using Ca2+ Gradients for Signaling.
The cytoplasmic Ca2+ level is low in resting cells.Clapham DE.Calcium Signaling. Cell. 2007. Dec 14;131(6):1047-58.
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Maintaining and Using Ca2+ Gradients for Signaling. The core of the Ca2+ signaling network. In excitatory Ca2+ signaling, plasma membrane ion channels are triggered to open by changes in voltage,or extra- or intracellular ligand binding.
Clapham DE.Calcium Signaling. Cell. 2007. Dec 14;131(6):1047-58.
When open, ~1 million Ca2+ ions/s/channel flow down the 20,000 fold [Ca2+]i gradient (ECa~+150 mV). Initial increases in [Ca2+] trigger more release, primarily from ER via Ca2+ -sensitive ryanodine receptors (RyR).
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Boron pag.116
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Boron pag.116
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Boron pag.121
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Boron pag.121
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Boron pag.124
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Boron pag.125
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Permeabilitatea membranei
celulare depinde de:
-interacţiunea ionilor cu apa
-bistratul lipidic membranar
-canale ionice
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Boron pag.146
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Boron pag.130
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Boron pag.131
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Boron pag.131
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Aquaporina Boron pag.111
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timp (ms)
+20
- 60
Pm
(m
V)
Variaţia potenţialului de membrană în raport cu
activitatea celulei nervoase
repolarizaredepolarizare
hiperpolarizare
depolarizare
repolarizare
Nerst
Vm = lnzXF
RT [X]i
[X]o
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Potenţial de acţiune
50
0
m
V PA
Na+
K+
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Boron pag.143
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…Due to its ability to give rise to spontaneous activity, the brain does not simply process information but also generates information.
György Buzsáki
...spontaneous neuron activity, far from being mere noise, is actually the source of cognitive abilities.
...the source of spontaneous neuron activity (noise), has never been identified and has been assumed to result from brain’s imperfections.
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Celule miocardice embrionare izolate în cultură. Imediat după punerea în
cultură se observă contracția celulelor individuale, la diferite ritmuri,
Ritmicitate...
http://www.cellsalive.com/myocyte.htm
Dupa 2-3 zile în vitro, miocitele se conectează prin joncțiuni gap, care asigură
activarea și contracția lor sincronă.
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Signal processing methods were used to reject the external and internal interferences, to visualize uterine activity, and to detect activity of fetal heart and brain.
A simulation study was carried out for a scanner with an array of magnetic field sensors placed all around the torso from the chest to the hip within a horizontal magnetic shielding enclosure
•S. Lew. Toward noninvasive monitoring of ongoing electrical activity of humanuterus and fetal heart and brain. Clinical Neurophysiology 128 (2017) 2470–2481
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Ritmicitate, activitate neuronală spontană (ANS)
Semnificație funcțională
- cardiovascular
- respirator
- digestiv
-endocrin
- ritm circadian
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-excitabilitate
Funcțiile transportului ionic transmembranar
-reglare metabolică
-cuplare metab.-excitabilitate
-metab. neurotransmițători
-presiune osmotică, volum celular
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Fiziologia este cea mai integrativă știință a Ființei Umane