Download Communication between cells

Communication
Communication between cells
2/15
• in multicellular organisms cellular functions
must be harmonized
• communication can be direct and indirect
• direct communication: through gap junction
• 6 connexin = 1 connexon; 2 connexon = 1 pore

• diameter 1.5 nm, small organic molecules
(1500 Ms) (IP3, cAMP, peptides) can pass
• called electric synapse in excitable cells
(invertebrates, heart muscle, smooth muscle,
etc.)
• fast and secure transmission – escape
responses: crayfish tail flip, Aplysia ink
ejection, etc.
• electrically connected cells have a high
stimulus threshold
Indirect communication
3/15
• through a chemical substance - signal
• signal source - signal - channel - receptor
• there are specialized signal sources (nerveand gland cells), but many cells do release
signals (e.g. white blood cells)
• the chemical character of the signal shows a
huge variety:
– biogenic amines: catecholamines (NA, Adr, DA),
serotonin (5-HT), histamine, esters (ACh), etc.
– amino acids: glu, asp, thyroxin, GABA, glycine,
etc.
– small peptides, proteins: hypothalamic hormones,
opioid peptides, etc.
– nucleotides and their derivates: ATP, adenosine,
etc.
– steroids: sex hormones, hormones of the adrenal
gland, etc.
– other lipophilic substances: prostaglandins,
cannabinoids
Classification by the channel
4/15
• this is the most common classification
• neurocrine
–
–
–
–
signal source: nerve cell
channel: synaptic cleft - 20-40 nm
reaches only the postsynaptic cell (whispering)
the signal is called mediator or neurotransmitter
• paracrine (autocrine)
– signal source: many different types of cells
– channel: interstitial (intercellular) space
– reaches neighboring cells (talking to a small
company)
– the signal sometimes is called tissue hormone
• endocrine
– signal source: gland cell, or nerve cell
(neuroendocrine)
– channel: blood stream
– reaches all cells of the body (radio or TV broadcast)
– the signal is called hormone 
Receptor types
5/15
• hydrophilic signal – receptor in the cell
membrane
• lipophilic signal – receptor in the plasma
• the first modifies existing proteins, the second
regulates protein synthesis 
• the membrane receptor can be internalized and
can have plasma receptor as well (endocytosis)
• membrane receptor types:
– ion channel receptors (ligand-gated channels)
on nerve and muscle cells – fast neurotransmission also called ionotropic receptor
– G-protein associated receptor – this is the most
common receptor type - on nerve cells it is called
metabotropic receptor – slower effect through
effector proteins – uses secondary messengers 
– catalytic receptor, e.g. tyrosine kinase – used by
growth factors (e.g. insulin) - induces
phosphorylation on tyrosine side chains
Neurocrine communication I.
6/15
• Otto Loewi, 1921 - vagusstoff
• frog heart + vagal nerve – stimulation
decreases heart rate, solution applied to
another heart – same effect – signal: ACh
• neuromuscular junction (endplate), signal: ACh
• popular belief: ACh is THE excitatory mediator
• in the muscle, it acts through an ionotropic
mixed channel (Na+-K+) – fast, < 1 ms
• later: inhibitory transmitters using Cl- channels
• even later: slow transmission (several 100 ms),
through G-protein mechanism
• neurotransmitter vs. neuromodulator
• Dale’s principle: one neuron, one transmitter,
one effect
• today: colocalization is possible, same
transmitters are released at each terminal
7/15
Neurocrine communication II.
• good example for the fast synapse: motor
endplate, or neuromuscular junction , 
• curare (South-American poison) ACh antagonist
• agonists and antagonists are very useful tools
• EPSP = excitatory synaptic potential
• IPSP = inhibitory synaptic potential
• reversal potential – sign changes – which ion is
involved
• effect depends also on the gradient – e.g. Cl• inhibition by opening of Cl- channel:
hyperpolarization or membrane shunt
• presynaptic and postsynaptic inhibition
• transmitter release is quantal: Katz (1952) –
miniature EPP, and Ca++ removal + stimulation
• size of EPSPs (EPPs) changes in small steps
• the unit is the release of one vesicle, ~10.000
ACh molecules
• elimination: degradation, reuptake, diffusion 
8/15
Integrative functions
• signal transduction is based on graded and
all-or-none electrical and chemical signals
in the CNS 
• neurons integrate the effects 
• spatial summation - length constant 
• determines: sign, distance from axon hillock

• temporal summation – time constant 
• summed potential is forwarded in frequency
code – might result in temporal summation

• release of co-localized transmitters –
possibility of complex interactions 
9/15
Plasticity in the synapse
• learning and memory is based on neuronal
plasticity
• plasticity is needed to learn specific sequence
of movements (shaving, playing tennis, etc.)
• formation of habits also depends on plasticity
• it is also needed during development (some
connections are eliminated)
• always based on feedback from the
postsynaptic cell
• mechanism in adults: modification of synaptic
efficacy
10/15
D.O. Hebb’s postulate (1949)
• effectiveness of an excitatory
synapse should increase if
activity at the synapse is
consistently and positively
correlated with activity in the
postsynaptic neuron
11/15
Types of efficacy changes
• both pre-, and postsynaptic mechanisms
can play a role
• few information about postsynaptic changes
• homosynaptic modulation
– homosynaptic facilitation: frog muscle – fast,
double stimulus – second EPSP exceeds temporal
summation – effect lasts for 100-200 ms 
– it is based on Ca++ increase in the presynaptic
ending 
– posttetanic potentiation – frog muscle stimulated
with long stimulus train - depression, then
facilitation lasting for several minutes 
– mechanism: all vesicles are emptied (depression)
then refilled while Ca++ concentration is still
high (facilitation)
12/15
Heterosynaptic modulation
• transmitter release is influenced by
modulators released from another synapse
or from the blood stream
• e.g. serotonin – snails and vertebrates
octopamine - insects
NA and GABA - vertebrates
• presynaptic inhibition belongs here
• excitatory modulation
– heterosynaptic facilitation - Aplysia –
transmission between sensory and motor neurons
increases in the presence of 5-HT
mechanism: 5-HT - cAMP - KS-channel closed AP longer, more Ca++ enters the cell 
– long-term potentiation - LTP e.g. hippocampus
increase in efficiency lasting for hours, days,
even weeks, following intense stimulation
always involves NMDA receptor 
G-protein associated effect
• called metabotropic receptor in neurons
• always 7 transmembrane regions - 7TM
• it is the most common receptor type
• ligand + receptor = activated receptor
• activated receptor + G-protein = activated
G-protein (GDP - GTP swap)
• activated G-protein - -subunit dissociates
• -subunit – activation of effector proteins
• -subunit - GTP degradation to GDP – effect
is terminated
13/15
Effector proteins
• Ca++ or K+-channel - opening 
• action through a second messenger
• Sutherland 1970 - Nobel-prize - cAMP
system
• further second messengers 
• modes of action:
– cAMP 
– IP3 - diacylglycerol 
– Ca++ 
•
•
•
•
one signal, several modes of action
one mode of action, several possible signals
importance: signal amplification 
effect is determined by the presence and
type of the receptor: e.g. serotonin
receptors 
14/15
15/15
Catalytic receptors
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 9-20.
End of text
Gap junction
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 4-33.
Classification by the channel
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 8-1.
Fast and slow neurotransmission
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-12.
The neuromuscular junction
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-13.
The endplate
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-14.
Signal elimination
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-31,34.
Spread of excitation in the CNS
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-1.
AP generation at axon hillock
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-43.
Spatial summation
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-44.
Summation of EPSP and IPSP
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-45.
Temporal summation
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-46.
Frequency code
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-47.
Neuromodulation
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-40,41.
Homosynaptic facilitation
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig.6-48.
Ca++-dependency of facilitation
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-49.
Posttetanic potentiation
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-50.
Heterosynaptic facilitation
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-51.
Long-term potentiation
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-52.
Lipid solubility and action
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 9-8.
Effector proteins: K+-channel
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-39.
Second messengers
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 9-10.
cAMP signalization
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 9-11.
Inositol triphosphate pathway
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 9-14.
Ca++ signalization
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 9-19.
Signal amplification
Alberts et al.: Molecular biology of the cell, Garland Inc., N.Y., London 1989, Fig. 12-33.
Serotonin receptors
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 1-4.