Slide 1 Chemical Synapses: Post-Synaptic Mechanisms ______
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Slide 1 Chemical synapses: post-synaptic mechanisms ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ Slide 2 Postsynaptic Membranes and ion channels ___________________________________ Ligand gated ion channels – a review ___________________________________ ___________________________________ a. Resting K+ channels: responsible for generating the resting potential across the membrane ___________________________________ b. Voltage- gated channels: responsible for propagating action potentials along the axonal membrane Two types of ion channels in dendrites and cell bodies are responsible for ___________________________________ generating electric signals in postsynaptic cells. (c) Has a site for binding a specific extracellular neurotransmitter (d) Coupled to a neurotransmitter receptor via a G protein. ___________________________________ ___________________________________ Slide 3 More things to know about Ion channels ___________________________________ All the ion channels in question have a common feature • A pore that allows the ion(s) in question to flow across the lipid bilayer The pore is specific to a certain ion or ions ___________________________________ • Leak K+ channel only allows K+ ions to flow across the membrane • Example: Acetylcholine (ACH) receptor allows Na+ to flow and the - glycine receptor allows Cl to flow through the channel ___________________________________ • Ligand gated ion channels are different than voltage-gated ion channels in that they are chemically gated ie via neurotransmitters Binding a small chemical triggers the opening of the ion channel ___________________________________ • i) Na+ channels - excitatory (generates an excitatory postsynaptic potential) ii) Cl- channels - inhibitory (generates an inhibitory postsynaptic potential) ___________________________________ • Important: The specificity of a transmitter response is a function of the receptor type NOT the transmitter itself. (i.e. Ach can be excitatory when binding to one type of AchR (NMJ)) and inhibitory when binding to another type of receptor ___________________________________ ___________________________________ Slide 4 Acetylcholine – general info ___________________________________ • Motor neuron transmitter at the neuromusccular junction (NMJ) in vertebrates • Present in brain (10% of synapses) ___________________________________ • Packaged in high numbers in vesicles 1,000 to 10,000 molecules per vesicle at the NMJ • Like all small chemical transmitters Ach is ___________________________________ synthesized and packaged into vesicles in the synapse • The NMJ pre-synaptic side is packed full of vesicles in the axon terminal • Many vesicles are released per action ___________________________________ potential to ensure a large safety margin so that the muscle fiber (i.e. the postsynaptic cell) will depolarize to beyond threshold. ___________________________________ ___________________________________ ___________________________________ Slide 5 Acetylcholine – receptor ___________________________________ • Officially called the nicotinic ACH receptor (nAChR) because nicotine binds to this receptor and activates it • ligand gated ion channel ___________________________________ • has a depolarizing effect because Na+ is the dominant ion through these channels ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ Slide 6 Acetylcholine – receptor ___________________________________ • generates an excitatory postsynaptic potential which at the NMJ (motor end plate) is often called an "end plate potential“ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ Slide 7 EPP - end plate potential ___________________________________ Aka Excitatory Junctional Potential (EJP) ___________________________________ ___________________________________ ___________________________________ ___________________________________ End plate potentials (EPPs) evoked by stimulation of a motor neuron are normally above threshold and therefore produce an action potential in the postsynaptic muscle cell. ___________________________________ ___________________________________ Slide 8 nACHR – a closer look ___________________________________ • Most of the mass of the protein protrudes from the outer (synaptic) surface of the plasma membrane • The M2 alpha helix (red) in each subunit is part of the lining of the ion channel ___________________________________ • Aspartate and glutamate side chains at both ends of each M2 helix form two rings of negative charges that help exclude anions from and attract cations to the channel. The gate, which is opened by binding of acetylcholine, lies within the pore. ___________________________________ ___________________________________ Aspartate ___________________________________ ___________________________________ ___________________________________ Slide 9 The Neuromuscular junction ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ Slide 10 The Neuromuscular junction ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ Slide 11 The Neuromuscular junction ___________________________________ • Arrival of an action potential at the terminus of a presynaptic motor neuron induces opening of voltage-gated Ca2+ channels • subsequent release of acetylcholine, which triggers opening of the ligand-gated nicotinic receptors in the muscle plasma membrane ___________________________________ • The resulting influx of Na+ produces a localized depolarization of the membrane • leading to opening of voltage-gated Na+ channels and generation of an action potential ___________________________________ * ___________________________________ * * ___________________________________ ___________________________________ ___________________________________ Slide 12 Synapses in the brain or central nervous system (CNS) ___________________________________ • A single synapse on a target is seldom found in brain • Large neurons in the brain typically receive many inputs (1000 to 80,000 per cell) ___________________________________ • The inputs are integrated in the receiving neuron such that a "decision" is made to pass on the information onto other cells - this "decision" is often whether or not to generate an action potential • each synaptic input usually only gives only a small depolarization, so ___________________________________ many inputs must cooperate (summate) to reach threshold to fire an action potential ___________________________________ ___________________________________ ___________________________________ ___________________________________ Slide 13 EPSP ___________________________________ An excitatory impulse, an excitatory post-synaptic potential raises the membrane potential above rest 1. An excitatory impulse at a synapse on the soma causes a depolarization of the whole soma including the beginning of the axon. ___________________________________ This is because the diameter of the soma or cell body is so large that the internal resistance is very low so current flow extremely well through the cell body The beginning of the axon is also known as the spike initialization zone or axon hillock and is packed with Na+ channels, an epsp of +15 to +20 ___________________________________ mV triggers an action potential in the zone 2. An epsp generated on a dendrite will diminish in strength by the time the current has reached the soma such that an epsp in a dendrite has less of a chance of triggering an action potential than an epsp ___________________________________ generated at the soma Due to the absence of voltage-gated Na+ channels in the soma and dendrite of most neurons it is very unlikely that an action potential will be generated in these regions ___________________________________ ___________________________________ ___________________________________ Slide 14 IPSP ___________________________________ • An inhibitory impulse is called an ipsp (inhibitory post-synaptic potential) and lowers the membrane potential below rest (hyperpolarizes) • Synaptic transmission triggers the opening ligand gated Cl- channels or ___________________________________ indirectly through other mechanisms the opening of K+ channels • Cl- flows into the cell • K+ flows out of the cell • Both increase the negative charge within the cell, hyperpolarizes the ___________________________________ soma • Brings membrane potential further away from threshold and so it is harder to trigger an action potential therefore inhibitory • An ipsp on the dendrite will have less effect due to current loss than an ___________________________________ ipsp in the soma ___________________________________ ___________________________________ ___________________________________ Slide 15 CNS ___________________________________