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Communication

Communication. 2 / 15. 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 

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Communication

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  1. Communication

  2. 2/15 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. 4-33.

  3. 3/15 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

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

  5. 5/15 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. Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-12.

  6. 6/15 Neurocrine communication I. • 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. 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  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. 6-13. Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-14.

  8. 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  Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-40,41. Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-47. Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-45. Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-44. Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-43. 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. 6-46.

  9. 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. 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. 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) Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-50. Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig.6-48. Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-49.

  12. 12/15 Heterosynaptic modulation • 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  Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-52. Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-51.

  13. 13/15 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. 14/15 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  Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 9-19. Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 1-4. Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 9-10. Alberts et al.: Molecular biology of the cell, Garland Inc., N.Y., London 1989, Fig. 12-33. Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-39. Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 9-14. Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 9-11.

  15. 15/15 Catalytic receptors Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 9-20.

  16. End of text

  17. Gap junction Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 4-33.

  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. 6-12.

  20. The neuromuscular junction Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-13.

  21. The endplate Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-14.

  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. 6-43.

  25. Spatial summation Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-44.

  26. Summation of EPSP and IPSP Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-45.

  27. Temporal summation Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-46.

  28. Frequency code Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-47.

  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. 6-49.

  32. Posttetanic potentiation Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-50.

  33. Heterosynaptic facilitation Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-51.

  34. Long-term potentiation Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-52.

  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. 6-39.

  37. Second messengers Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 9-10.

  38. cAMP signalization Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 9-11.

  39. Inositol triphosphate pathway Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 9-14.

  40. Ca++ signalization Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 9-19.

  41. Signal amplification Alberts et al.: Molecular biology of the cell, Garland Inc., N.Y., London 1989, Fig. 12-33.

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

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