1. Communication

2. Communication between cells
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Communication between cells
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
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig

3. Indirect communication
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through a chemical substance - signal
signal source - signal - channel - receptor
there are specialized signal sources (nerve- and 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

4. Classification by the channel
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this is the most common classification
neurocrine
signal source: nerve cell
channel: synaptic cleft 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 
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 8-1.

5. Receptor types hydrophilic signal – receptor in the cell membrane
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig
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Receptor types
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
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 9-8.

6. Neurocrine communication I.
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Neurocrine communication I.
Otto Loewi, 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. Neurocrine communication II.
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig
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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, ~ ACh molecules
elimination: degradation, reuptake, diffusion 
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-31,34.
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig

8. Integrative functions
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig
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Integrative functions
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-1.
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig
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 
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-40,41.

9. Plasticity in the synapse
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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. 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. Types of efficacy changes
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig
11/15
Types of efficacy changes
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig.6-48.
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 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)
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig

12. Heterosynaptic modulation
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig
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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 
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig

13. G-protein associated effect
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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

14. Effector proteins Ca++ or K+-channel - opening 
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig
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Effector proteins
Ca++ or K+-channel - opening 
action through a second messenger
Sutherland 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 
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig
Alberts et al.: Molecular biology of the cell, Garland Inc., N.Y., London 1989, Fig
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 1-4.

15. 15/15
Catalytic receptors
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig

16. End of text

17. Gap junction
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig

18. Classification by the channel
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 8-1.

19. Fast and slow neurotransmission
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig

20. The neuromuscular junction
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig

21. The endplate
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig

22. Signal elimination
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-31,34.

23. Spread of excitation in the CNS
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-1.

24. AP generation at axon hillock
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig

25. Spatial summation
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig

26. Summation of EPSP and IPSP
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig

27. Temporal summation
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig

28. Frequency code
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig

29. Neuromodulation
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-40,41.

30. Homosynaptic facilitation
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig.6-48.

31. Ca++-dependency of facilitation
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig

32. Posttetanic potentiation
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig

33. Heterosynaptic facilitation
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig

34. Long-term potentiation
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig

35. Lipid solubility and action
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 9-8.

36. Effector proteins: K+-channel
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig

37. Second messengers
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig

38. cAMP signalization
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig

39. Inositol triphosphate pathway
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig

40. Ca++ signalization
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig

41. Signal amplification
Alberts et al.: Molecular biology of the cell, Garland Inc., N.Y., London 1989, Fig

42. Serotonin receptors
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 1-4.