EE3DBE9Fd01 - Molecular signaling in the neuron General...

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1 1 Molecular signaling in the neuron • General principles of cell signaling • Ion channels • Membrane potential (resting – action potential) • Synaptic transmission – Electrical – Chemical • NMJ • CNS 2 Synaptic integration Synaptic transmission between neurons at CNS is much more complex than at NMJ: -central neuron receives inputs from hundreds of other neurons -central neuron receives both excitatory and inhibitory signals -central neuron must integrate diverse incoming signals and decide if it will fire an action potential or not Synaptic transmission at NMJ is very efficient b AP in presynaptic cell leads to AP in postsynaptic cell B in CNS individual PSP are way too small (around 0.2 mV) to generate action potential => individual PSP’s are summed to total net PSP that arrives through passive propagation in cell body
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2 3 •Sculpturing role of inhibition (inhibitory synaptic potential) •The effect of a synaptic potential is determined not by the type of transmitter released, but by the type of ion channels gated by the transmitter in the postsynaptic cell: most transmitters are recognized by receptors that mediate either excitatory or inhibitory potentials * neurons that release glutamate : act on receptors that produce excitation * neurons that release GABA or glycine : act on ionotropic inhibitory receptors Inhibitory and excitatory neurotransmitters 4 Three classes of glutamate receptors conduct both Na + and K + The non-NMDA receptors are important for the early component of the EPSP in motor neurons The NMDA-receptors are important for the late component of the EPSP response and also have a major role in long term potentiation (LTP)
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3 5 Inhibitory synaptic action: GABA- and glycine-gated channels – Cl- GABA binds to ionotropic Cl - channels or metabotropic K + -channels, glycine binds ionotropic Cl - channels the Cl - channels allow Cl - to flow in => hyperpolarisation the K + -channels allow K + to flow out => hyperpolarisation 6 Inhibitory synaptic action: GABA- and glycine-gated channels – Cl- I EPSP = g EPSP x (V m – E EPSP )
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4 7 Structure of glutamate, GABA- and glycine-gated channels 8 GABA- and glycine-gated channels: role in disease - abuse GABA-gated channel is target for GABA benzodiazepines anti-anxiety and muscle relexant ex. Xanax, valium, ativam,. .. barbiturates mild sedation – total anesthesia alcohol b Reducing brain activity b Valproate b used for the treatment of migraines and bipolar disorder (depression) b Mechanism?? b increasing the concentration of GABA
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5 9 GABA- and glycine-gated channels: role in disease - abuse 10 Neuronal integration: introduction A cell at any given moment has two options : to fire or not to fire. This decision-making = the brain’s most fundamental operation
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This note was uploaded on 05/28/2010 for the course WE CHMOBI0000 taught by Professor Geertvanloo during the Spring '10 term at Ghent University.

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EE3DBE9Fd01 - Molecular signaling in the neuron General...

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