Electrical Activity of Nerve Cells 
Paul R. Adams, Ph.D. — Investigator 
Dr. Adams is also Professor of Neurobiology and Behavior and of Pharmacological Sciences 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 
postdoctoral 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 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, sodium, 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. 
There are many types of potassium channel, 
differing according to their molecular structure 
(see the articles in this volume by Richard 
Aldrich and Lily Jan), speed of opening and clos- 
ing, and the way in which their gates are con- 
trolled. We are studying potassium channels in 
bullfrog sympathetic ganglion cells to under- 
stand better how they are controlled and how 
they contribute to the electrical activity of nerve 
cells. We have been particularly intrigued by a 
channel we call the M channel. This channel is 
turned off as a result of the binding of certain 
neurotransmitters (chemicals released from 
nerve endings) to receptors on the cell surface. 
As a result, less potassium leaves the cell, which 
is therefore less negative and more able to fire 
electrical pulses. Tumofif of this channel occurs 
via activation of a G protein (see the article by 
John Exton) . However, after the neurotransmitter 
has been removed, M channels turn back on and 
transiently become more numerous than initially 
observed. We have shown that calcium and ara- 
chidonic acid are involved in this overshooting 
response. Various levels of calcium were per- 
fused into nerve cells while they were visualized 
with a special calcium-detecting microscope. 
Neurotransmitter stimulation of receptors pro- 
duces a small calcium signal that is sufficient to 
increase the activity of M channels. However, this 
is not seen until the concomitant G protein- 
mediated suppression of the channels is termi- 
nated by removing the transmitter. 
M channels work in concert with many other 
types of channels, which we have also character- 
ized. This information can then be combined 
with studies of calcium diffusion and membrane 
geometry to predict completely the cell's electri- 
cal output. We are making detailed quantitative 
morphological measurements of cells that have 
been previously characterized electrophysiologi- 
cally in both bullfrog ganglia and mammalian 
hippocampus and lateral geniculate. This is 
achieved by automatic three-dimensional recon- 
struction of dye-filled cells, which are optically 
sectioned using confocal microscopy. Our voxel- 
based reconstructions, developed in collaboration 
with the computer science department at Stony 
Brook, can then be used as a platform for Monte 
Carlo simulations of the movements of single ions 
in small cell structures, such as dendritic spines. 
