Communication

Communication between cells 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.

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

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  Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 8-1.

Receptor types hydrophilic signal – receptor in the cell membrane Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-12. 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.

Neurocrine communication I. 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

Neurocrine communication II. Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-14. 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.

Integrative functions 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. 6-45. 8/15 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. 6-46. 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. 6-47. Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-40,41.

Plasticity in the synapse 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

Types of efficacy changes Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 6-49. 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 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.

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

G-protein associated effect 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

Effector proteins Ca++ or K+-channel - opening  Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 9-11. Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 9-10. 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. 9-14. 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. 9-19. 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. 1-4.

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.