NRSC 407

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NRSC 407 September 25, 2007 Presynaptic
Mechanisms
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In-Class Exercise
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The quantal nature of transmitter release (a)
Discovery of miniature endplate potentials
(mepps) 1952 (Fatt Katz)
small-amplitude (ca. 1 mV) depolarizations
occur at motor endplate (postsynaptic membrane)
but not elsewhere spontaneous (not evoked)
same time course as evoked synaptic
potentials _______________________________________
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Some pharmacology of nicotinic cholinergic
synapses (e.g. frog nmj)
release blocked by botulinum toxin, triggered
by a-latrotoxin
nAChRs blocked by curare, a-bungarotoxin, etc.
ACh hydrolysis by acetylcholinesterase (AChE)
blocked by prostigmine, eserine, edrophonium,
etc.
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Mepps at frog nmj same pharmacology as epps
(epsps)
frog NMJ
prostigmine
Nicholls 11.7
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Quantal Hypothesis (Katz coworkers) the
single quantal events observed to occur
spontaneously are the building blocks for
synaptic potentials evoked by stimulation
Test of this theory statistical analysis of the
epp (Del Castillo Katz)
(a) nerve terminal contains very many pre-formed
quantal packets of ACh n each of which has
a probability p of being released in response
to nerve action potential
(b) quanta are released independently
(c) therefore, with many trials, mean number of
quanta released per trial m would be np
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and.. (d) the number of times the response
consisted of 0,1,2,3,x quanta would be
given by the binomial distribution
But Del Castillo Katz could not measure n or p
experimentally, so they reasoned that they could
make p very small by reducing the epp (using low
Ca, high Mg). Under those conditions, trials
yield mostly 0s (failures) with occasional 1s,
2s, 3s etc.
In that case (with p very small), the number of
quanta (x) that constitute the reduced epp (in
many observations) should be predicted by
Poissons Law. Poisson distribution an
approximation to binomial distribution when p is
very small.
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reduced epps at frog nmj in low-Ca medium (to
lower release)
observe stepwise fluctuations in reduced epp
Nicholls 11.8 A
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To predict a Poisson distribution, one doesnt
need to know n or p need to measure only their
product np m, the mean number of quanta
released per trial (i.e. the quantal
content) nx N(mx/x!)em where nx is
the number of times response consists of x quanta
N is number of trials
To measure m m (mean amplitude of reduced
epp) / (mean amplitude of mepp) When x 0 (i.e.
a failure), n0 Nem , so m ln (N/n0)
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In-Class Exercise
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