Communication

1
Communication
2
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

3
Indirect communication
3/15

• 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
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 ?

5
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

6
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, lt 1 ms
• later inhibitory transmitters using Cl- channels
• even later slow transmission (several 100 ms),
  through G-protein mechanism
• neurotransmitter vs. neuromodulator
• Dales principle one neuron, one transmitter,
  one effect
• today colocalization is possible, same
  transmitters are released at each terminal

7
Neurocrine communication II.
7/15

• 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
Integrative functions
8/15

• 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
Plasticity in the synapse
9/15

• 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
D.O. Hebbs postulate (1949)
10/15

• 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
11/15

• 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
Heterosynaptic modulation
12/15

• transmitter release is influenced by modulators
  released from another synapse or from the blood
  stream
• e.g. serotonin snails and vertebratesoctopamine
  - insectsNA and GABA - vertebrates
• presynaptic inhibition belongs here
• excitatory modulation
• heterosynaptic facilitation - Aplysia
  transmission between sensory and motor neurons
  increases in the presence of 5-HTmechanism 5-HT
  - cAMP - KS-channel closed - AP longer, more Ca
  enters the cell ?
• long-term potentiation - LTP e.g.
  hippocampusincrease in efficiency lasting for
  hours, days, even weeks, following intense
  stimulationalways involves NMDA receptor ?

13
G-protein associated effect
13/15

• 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
14/15

• 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 ?

15
Catalytic receptors
15/15
Eckert Animal Physiology, W.H.Freeman and Co.,
N.Y.,2000, Fig. 9-20.
16
End of text
17
Gap junction
18
Classification by the channel
19
Fast and slow neurotransmission
20
The neuromuscular junction
21
The endplate
22
Signal elimination
23
Spread of excitation in the CNS
24
AP generation at axon hillock
25
Spatial summation
26
Summation of EPSP and IPSP
27
Temporal summation
28
Frequency code
29
Neuromodulation
30
Homosynaptic facilitation
31
Ca-dependency of facilitation
32
Posttetanic potentiation
33
Heterosynaptic facilitation
34
Long-term potentiation
35
Lipid solubility and action
36
Effector proteins K-channel
37
Second messengers
38
cAMP signalization
39
Inositol triphosphate pathway
40
Ca signalization
41
Signal amplification
42
Serotonin receptors