INTER-CELLULAR CONTACT
MECHANICAL COUPLING
• desmosomes (macula adherens; cell adhesion and mechanical
stability of tissues) – epidermis, liver, myocardium
ELECTRICAL COUPLING
• gap junction (nexus) (in intercalar disc; consists of conexons)
CONEXON
OPEN CLOSED
6 subunits
1-2 nm central channel
HUMORAL COUPLING (REGULATION)
autocrine
paracrine
endocrine
NERVOUS COUPLING (REGULATION)
Receptor, ligand, second messenger.
Neurotransmitters vs. tissue „hormones“ vs. hormones.
Integration of humoral and nervous regulations in organism.
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
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 pumps (K+, Ca2+)
Gs: glucagon, oxytocin, histamine, dopamine, ADH, FSH, TSH, AD (b1,2)
Gi: Ach, opioids, AGII, AD (a2), dopamine
IP3
H-R complex binds to G-protein – p
Activation phospholipase C PIP2 IP3 and DAG
DAG: activates proteinkinase C
Phosphorylation of Na+/H+ pump pHi
Effect of prostaglandines and prostacyclines
IP3: translocation to endoplasmic reticulum
Increase in cytoplasmic availability of calcium
„third messenger“
AD (a1), Ach, thyroliberin, ADH, tromboxans
IONIC CHANNELS
Membránová elektrofyziologie myokardu, P. Pučelík, Avicenum, 1990
Molecular biology of the cell. B. Alberts et al., Garland Science2002
CHANNELS WITHOUT GATES
GATED CHANNELS
1. LIGAND GATED CHANNELS (nicotinic cholinergic receptor;
ATP-sensitive K+ channel)
2. G-PROTEIN GATED CHANNELS (Ach-sensitive K+ channel
of SA node – muscarinic receptor)
3. MECHANICALLY GATED CHANNELS – „stretch“ receptors
(K+ , Ca2+)
4. VOLTAGE GATED CHANNELS
• One-gate channels (activation vs. deactivation)
• Two-gates channels (activation vs. inactivation vs. recovery from
inactivation)
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 membrane
mechanisms.
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.
EQUILIBRIUM POTENTIAL
NERNST EQUATION
EP = (R . T / n . F) . ln Xe / Xi
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).
PHYSIOLOGICAL SIGNIFICANCE OF RESTING
MEMBRANE POTENTIAL
Possibility to code and transmit information in living systems
(excitable tissues) – in the way of action potential
Triggering muscle contraction
ACTION POTENTIAL
LOCAL RESPONSE
Changes of conductivity of the membrane for particular ions
(opening the ion-specific channels)
Depolarization, transpolarization, repolarization.
Inward currents x outward currents.
ms
mV
ms
mV
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