Marie Nováková, 2020-20211
PHYSIOLOGY OF THE CELL
Seminar I.
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ligand
hydrophilic
glycocalyx ion
hydrophobic
I – integral protein
R – receptor
E – enzyme
K – channel (kanál)
P – transporters, e.g. ATP-ase (pumpa)
Membrane
lipids
Proteins
PLASMATIC MEMBRANE
INTER-CELLULAR CONTACT
MECHANICAL COUPLING
• desmosomes (macula adherens; cell adhesion and mechanical stability of tissues) –
epidermis, liver, myocardium
ELECTRICAL COUPLING
• gap junction (nexus), consists of two connexons, forms s.-c. electrical synapse (neuron)
CONNEXON
OPEN CLOSED
6 subunits, connexin
1-2 nm central channel
Marie Nováková, 2020-20213
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HUMORAL COUPLING (REGULATION)
autocrine
paracrine (neurocrine) juxtacrine
endocrine (neuroendocrine)
NERVOUS COUPLING (REGULATION)
Receptor, ligand, second messenger.
Neurotransmitters vs. tissue „hormones“ vs. „classic“ hormones
Integration of humoral and nervous regulations in organism
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1. Number of receptors
2. Number of ligands
3. Subtypes of receptors
4. Competition on receptors
5. Endogenous ligands, exogenous ligands
6. Orphan receptors
7. Placement of receptors
8. Convergence and divergence of the effects
9. Transmission of information intracellularly
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SECOND MESSENGER SYSTEMS
cAMP, cGMP, IP3, DAG, Ca2+-calmodulin
cAMP
H-R complex binds to G-protein – stimulatory or inhibitory
(a, b and g subunits)
Mg2+, HR b-g
Activation or inhibition of adenylcyclase cAMP
Activation of proteinkinases protein phosphorylation
Direct regulation of ionic channels and exchangers (K+, Ca2+)
Gs: glucagon, oxytocin, histamine, dopamine, ADH, FSH, TSH, AD (b1,2)
Gi: Ach, opioids, AGII, AD (a2), dopamine
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IP3 / DAG
H-R complex binds to G-protein – Gq
Activation of phospholipase C PIP2 IP3 and DAG
DAG: activates proteinkinase C
Phosphorylation of Na+/H+ pump pHi
Effect of prostaglandins and prostacyclin
IP3: translocation to endoplasmic reticulum
IP3 receptor (subtypes), opening of calcium channels
Increase in cytoplasmic availability of calcium - „third messenger“
Gq: AD (a1), Ach, thyreoliberin, ADH, thromboxane
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IONIC CHANNELS
Membránová elektrofyziologie myokardu, P. Pučelík, Avicenum, 1990
Molecular biology of the cell. B. Alberts et al., Garland Science 2002
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CHANNELS WITHOUT GATES
GATED CHANNELS
1. VOLTAGE GATED CHANNELS
• One-gate channels (activation vs. deactivation)
• Two-gates channels (activation vs. inactivation vs. recovery from inactivation)
2. LIGAND GATED CHANNELS (nicotinic cholinergic receptor; ATP-sensitive K+ channel)
3. G-PROTEIN GATED CHANNELS (Ach-sensitive K+ channel of SA node – muscarinic
receptor)
4. MECHANICALLY GATED CHANNELS – „stretch receptors“ (K+ , Ca2+)
Marie Nováková, 2020-202110
RESTING MEMBRANE POTENTIAL
DIFUSSION CURRENTS: ionic currents across the membrane (in both directions) through
open ionic channels (specific channels) = simple diffusion according to concentration
gradient
= difference between electrical potential of intra- and extracellular solution (at rest).
Different composition of IC and EC environment is kept by membrane transport
mechanisms.
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ELECTROCHEMICAL GRADIENT
• semipermeable membrane
• different conductivity for ions
• the force given by concentration gradient equals to the force given by electrical gradient
DONNAN EQUILIBRIUM (D. PHENOMENON)
Concentration of anions multiplied by concentration of cations on one side of membrane
equals to concentration of anions multiplied by concentration of cations on the other side
of membrane.
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3 2
ATP
ase
Na+
K+
150mM
155mM
+ + + + + + + + + + + + + + + + +
- - - - - - - - - - - - - - - - - - - - - - - Na+
K+
Concentration gradient
Electrical gradient
Nernst equation:
Ex =
R . T (Cxout)
F (Cxin)
ln
ENa = +40 mV
EK = -90 mV
ECl = -70 mV
ECa = +60 mV
Ix = gx . (E - Ex)
I – current, E – voltage, g – specific voltage and time-dependent conductance
RESTING MEMBRANE VOLTAGE
Er = -85 mV
Equilibrium potential
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GOLDMAN (HODGKIN-KATZ) EQUATION
MP = gK . EK + gNa . ENa + gCl . ECl / gK + gNa + gCl
Respects the fact that even at rest there are membrane currents present –
background current (inward, outward).
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PHYSIOLOGICAL SIGNIFICANCE OF RESTING MEMBRANE POTENTIAL
Possibility to code and transmit information in living systems (excitable tissues) – in the form of
action potential
Triggering of muscle contraction by action potential!
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ACTION POTENTIAL
LOCAL RESPONSE
Changes of conductivity of the membrane for particular ions
(opening the ion-specific channels)
Depolarization, transpolarization, repolarization. REFRACTERITY.
Inward currents x outward currents.
ms
mV
ms
mV
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MUSCLE CONTRACTION AND RELAXATION
CONTRACTILE PROTEINS
ACTIN – globular, 400 molecules = chain = F-actin; 2 chains in spiral = filament
MYOSIN – „thick“ filaments, head with ATP-ase activity, filament = 150 – 360 molecules of myosin
(head + neck = heavy meromyosin, light meromyosin)
MODULATORY PROTEINS
TROPONIN – C, I, T
TROPOMYOSIN
PHYSIOLOGICAL ROLE OF CALCIUM
PRINCIPLE OF MUSCLE RELAXATION
Removal of calcium from cytoplasm
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