Electrical Activity of Nerve Cells 
Paul R. Adams, Ph.D. — Investigator 
Dr. Adams is also Professor of Neurobiology and Behavior, Pharmacology, and Neurology at the State 
University of New York at Stony Brook. He received his B.A. degree in physiology and pharmacology from 
Cambridge University and his Ph.D. degree in pharmacology from the University of London. His postdoc- 
toral work was done with Bert Sakmann at the Max Planck Institute, Gottingen, and with Philippe Ascher 
at the Ecole Normale, Paris. Dr. Adams is currently a MacArthur Fellow. He was recently elected Fellow 
of the Royal Society. 
NERVE cells are specialized to generate, trans- 
mit, and receive rapid electrical messages. 
Electrical impulses, called action potentials, last 
about 1,000th of a second and can travel along 
specialized nerve cell extensions at speeds over 
100 mph. Chemical transmitter substances re- 
leased onto the nerve cell by other nerve cells 
control the precise timing of these electrical 
pulses. We are trying to understand how these 
pulses are generated and how transmitters im- 
pinging on the cell control them. 
Cell membranes are normally effective barriers 
to the movement of ions (electrically charged 
atoms) between the cell environment and the 
cell interior. This insulating property allows the 
inside of a nerve cell to have a different electrical 
voltage from the outside, or from a neighboring 
cell. The electrical activities described above are 
regulated by special protein molecules, called 
ion channels, which are embedded in the cell 
membrane. There are many types of ion channel. 
Each type has a specific role, but all have in com- 
mon a unique feature that allows certain ions to 
travel easily through them. The protein chains 
that make up an ion channel molecule are 
arranged to create a minute tunnel, through 
which certain types of ions — for example, so- 
dium, potassium, or calcium ions — can quickly 
move. 
The direction that the ion moves is not con- 
trolled by the tunnel but by the ion concentra- 
tions and the transmembrane voltage. The tunnel 
does, however, control the type of ion that 
moves. Thus the sodium channel only allows so- 
dium ions to pass. Because sodium ions are abun- 
dant outside, but not inside, nerve cells, the exis- 
tence of open sodium channels leads to an inward 
stream of sodium ions, making the cell interior 
positive. On the other hand, when potassium 
channels open, potassium streams out of the cell, 
making it negative. Because these tunnels are not 
always open (indeed are closed most of the 
time), it is supposed that the channel must have 
some sort of gate. 
The basic electrical pulse of a nerve cell is a 
positive-negative sequence reflecting the rapid 
opening of sodium channels followed by their 
closing and the opening of potassium channels. 
What triggers the opening and closing of the ion 
channel gates? It has been known for some time 
that sodium channel opening is triggered by a pos- 
itive change in the membrane voltage. We have 
recently shown that an important trigger for po- 
tassium channel opening is a brief increase in cy- 
toplasmic calcium just beneath the cell mem- 
brane. Some of our most recent work has focused 
on how this cytoplasmic signal is generated. 
We have split the problem into two parts, using 
individual nerve cells isolated from bullfrogs. 
First we analyzed how calcium gets through the 
membrane from the outside. We employed the 
voltage-clamp technique, in which an electrical 
connection is made to the cell interior via a glass 
micropipette; this allows application of voltages 
to the cell and measurement of ion movements 
through channels. The conclusion from this 
study is that the cell membrane contains numer- 
ous channels specialized to allow calcium 
entry — channels that open quickly when the 
transmembrane voltage becomes positive and 
stay open as long as the voltage remains positive. 
Only one type of calcium channel seems to be 
operating (other scientists report a more compli- 
cated process in other tissues) . 
The second part of the problem was to deter- 
mine how calcium spreads within the cell. Here 
we used a calcium-sensitive fluorescent dye and a 
scanning laser microscope. The laser beam is fo- 
cused to a small spot, which can be rapidly 
scanned over the cell. For example, the spot can 
be scanned from membrane to membrane in a few 
thousandths of a second. We find that calcium 
moves quickly through the cytoplasm once it has 
entered through the open calcium channels. 
Computer calculations show that the move- 
ment of calcium can be accounted for by the fa- 
miliar physical process of diffusion, without any 
need for special mechanisms. Calcium move- 
ments, however, are modified to some extent by 
binding to cytoplasmic molecules (such as pro- 
teins, or the dye we introduced into the cell to 
measure calcium). 
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