Lecture 9 20 September 2005 Synaptic communication II: postsynaptic mechanisms in chemical synapses

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Lecture 920 September 2005Synaptic
communication IIpostsynaptic mechanismsin
chemical synapses
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MCB/BIOC/NRSC 407 20 September 2005
John Hildebrand Lecture 9 Synapses
II postsynaptic mechanisms in chemical
synapses   Reading assignment Nicholls 162-175
Kandel 197-215   I. Model synaptic
preparation vertebrate (frog) neuromuscular
junction (NMJ) organization and function of
this synapse (a) EPSP (EPP) (b)
neurotransmitter is acetylcholine (ACh)
nature of the EPP (a) electrotonic
character (b) relation between end-plate
current (EPC) and EPP (c) ionic basis of EPP  
II. Acetylcholine receptors (AChR)
patch-recording methods single-channel
events vs. macro physiology of the synapse   III.
Inhibitory synapses (a) IPSP KEY CONCEPT
reversal potential
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Nicholls 9.4 A
frog neuromuscular junction (nmj)
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Neurotransmitter at vertebrate neuromuscular
junction (nmj)
Acetylcholine (ACh)
O

(CH3)3NCH2CH2O-CCH3 X
ACh binds to nicotinic ACh receptors (nAChR) in
the postsynaptic (endplate) membrane.
Curare (South American arrowhead poison, active
component the alkaloid d-tubocurarine)
competitively blocks ACh binding to
nicotinic AChR
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Pharmacological isolation of the end-plate
potential (epp)
at vertebrate nmj, epp is depolarizing (excitatory
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treat preparation with low level of curare (to
reduce the number of functioning nAChRs) and thus
lower the epp
Kandel 12-5
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NOTE epp (end-plate potential) is a special
case of psp (post-synaptic potential) psp
applies to any chemical synapse epp applies only
to the end-plate (postsynaptic membrane) of a
muscle fiber . and two more important
abbreviations epsp excitatory post-synaptic
potential epc excitatory postsynaptic
current ipsp inhibitory post-synaptic
potential ipc inhibitory postsynaptic
current
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Nicholls 9.5
Synaptic potentials in a partially curarized
mammalian nmj
3 trials, 1 generating a spike (because epp
reduced to near threshold)
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Kandel 12-7
Relationship between epp and end-plate current
(epc)
note delay in postsynaptic response
Kandel 12-7
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Nicholls 9.6
Decay of psps (epps) with distance from the
end-plate region of muscle fiber
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Kandel 12-6
Decay of psp with distance from the muscle
endplate
Kandel 12-6
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Nicholls 9.7
Iontophoretic (ionophoretic) mapping of ACh
sensitivity (frog nmj)
ACh expelled from micropipette by passing
current
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Another nmj configuration in vertebrates (e.g.
snake skeletal muscle)
With the aid of collagenase treatment, nerve
terminal can be lifted off the muscle fiber.
Kandel 12-1
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Nicholls 9.9
Distribution of ACh sensitivity (AChRs) in
postsynaptic membrane
postsynaptic craters after removal of nerve
terminal
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nAChRs revealed at endplate of mouse
skeletal muscle by autoradiography using
125I-labeled a-bungarotoxin (which binds
specifically and tightly to nAChRs)
Kandel 12-2
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Kandel 12-4
Distribution of postsynaptic nAChRs presynaptic
Ca channels (revealed by fluorescent-labeled
toxins)
Kandel 12-4
(two patterns separated for clarity)
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Nicholls 9.11 A
Postsynaptic currents (epcs) studied by
voltage-clamp recording at the motor end plate
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Nicholls 9.11 B
Reversal potential in the voltage-clamped nmj
preparation
Reversal potential Vr for this synapse (nmj) is
0 mV
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Nicholls 9.11 C
Peak epc as a function of Vm - note reversal
potential (Vr)
Vr
outward current
inward current
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epp is produced by an epc due to the simultaneous
flow of both Na and K
Experiments have shown that 1) gNa gK both
increase simultaneously when ACh binds
to nAChRs
Vr
Vr
2) gCl is unaffected
3) the ACh-sensitive gNa gK are relatively
insensitive to Vm
Kandel 12-8
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Relationship between Vr for synaptic potential
and Vr for synaptic current
Kandel 13-8
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Nicholls 9.12 A
Electrical model of the postsynaptic (endplate)
membrane
for Vr 15 mV, ?gNa/?gK . 1.3 at the
vertebrate nmj
see Box 9.1 in Nicholls
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Error in Nicholls book In Box 9.1, at the
bottom of the left-hand column, the denominator
of the first fraction in the equation should be
?gK
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Nicholls 9.12 B
Simplified version of endplate model
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STUDY BOX 9.1 (p. 169) in Nicholls!! Na and K
move independently through same ACh receptor
channel, so can be represented by separate
conductances, gNa gK. ?INa ?gNa
(VmENa) ?IK ?gK (VmEK ) When Vm Vr
INa IK 0 , so INa IK Therefore
?gNa (VrENa) ?gK (VrEK) and so ?gNa /
?gK (VrEK) / (VrENa) (note error in
book!!) and finally. Vr ?gNaENa ?gKEK /
(?gNa ?gK)
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The nmj from ACh binding to muscle contraction
Kandel 12-16
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Nicholls 10.1 A
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12-9a
Patch recording from single ACh-activated channel
Kandel 12-9 A
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Behavior of individual nAChR channels revealed by
patch-clamp recording
Vm,rest 90 mV in B 130 mV in C
elementary current 2.69 pA (mean current
through the single type of channel present)
this current corresponds to an elementary
conductance of 30 pS
Kandel 12-9
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12-10
Single-channel current
same Vr as for macro- scopic epc!
Kandel 12-10
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Summary ACh-activated epp, epc, single-channel
current
Vr
Kandel 12-12
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Recall inhibitory interneurons in spinal cord
Nicholls 22.6
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Nicholls 9.14 A
Direct synaptic inhibition
IPSP
Vm(rest) 75 mV
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Nicholls 9.14 C
Partial, simplified electrical model of
motoneuron membrane
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Intracellular recording from a neuron in the
lamprey brainstem, which receives glycinergic
inhibitory synaptic input

• 3 intracellular
• electrodes used
• recording
• current-passing (brief hyperpolarizing pulses)
• iontophoretic pipet to deliver glycine

Nicholls 9.15
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Current-shunting effect of inhibitory synapses
Kandel 13-7