Zoo/Neuro/Psych 523 Lecture 20
Reading for lect 20 is pp 200 - 206.
The Role of Calcium in Release
The most important experiments on this topic were carried out on the squid giant synapse. This preparation
has the advantage that, unlike the frog neuromuscular junction, the presynaptic terminal is large enough to
penetrate with microelectrodes, so that the membrane potential can be measured and controlled; also
various interesting things can be injected into the nerve terminal directly from an intracellular electrode.
This preparation was used to answer several important questions, for example are action potential currents
that flow into the terminal necessary for transmitter release. This answer is NO! (If INa is blocked with
TTX, and the terminal is depolarized by passing current from an intracellular electrode, release still occurs.
Similarly, if IK is blocked with TEA or 4-AP, depolarization causes release. Therefore neither INa nor IK
are needed for release). However if I
is blocked by lowering external [Ca++] to zero, or by using a
specific Ca channel blocker, release is blocked.
The role of the action potential seems to be merely to depolarize the cell, and this depolarization produces
an increase in g
, so that Ca++ enters and release occurs.
If this hypothesis is correct, then the following should be true:
1. If Ca++ is injected directly into the terminal, transmitter release should be stimulated. Miledi showed
that this worked.
2. There should be a voltage sensitive Ca++ channel in the terminal. Katz and Miledi poisoned the squid
synapse with TTX and TEA to suppresses INa and IK, and found that when they depolarized the terminal, a
regenerative depolarizing current could be measured. Its amplitude depended on the external Ca++
concentration, and on the amount of depolarization up to a certain point and then decreased if the
depolarization was increased even more. Finally if they went all the way to 140 mV, no release occurred.
= 140 mV of course. If they gave the terminal a 140 mV depolarization, no release occurred, but
when the pulse was turned off, an enormous PSP occurred. This was because on going to 140 mV, g
turned on, but there is no I
(driving force is zero). On turning the pulse off, the Ca++ channels do not
close immediately, so a calcium current flows into the terminal and transmitter is released. There is a