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Communication. Communication between cells in multicellular organisms cellular functions must be harmonized communication can be direct and indirect direct.

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Presentation on theme: "Communication. Communication between cells in multicellular organisms cellular functions must be harmonized communication can be direct and indirect direct."— Presentation transcript:

1 Communication

2 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 2/15 Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig

3 Indirect communication 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 3/15

4 Classification by the channel 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 4/15 Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 8-1.

5 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 5/15 Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 9-8.

6 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 Dales principle: one neuron, one transmitter, one effect today: colocalization is possible, same transmitters are released at each terminal 6/15

7 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 7/15 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. 6-31,34.

8 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 8/15 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 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 Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-40,41.

9 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 9/15

10 D.O. Hebbs 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 10/15

11 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 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) 11/15 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

12 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 - K S -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 12/15 Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig

13 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

14 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 14/15 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 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 Catalytic receptors Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig /15

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.


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