THE ROLE AND CONTROL OF IONIC CHANNELS IN EXCITABLE CELLS 
Paul R. Adams, Ph.D., Investigator 
Work in Dr. Adams's laboratory is focused on the 
electrical properties of vertebrate nerve cells. Re- 
search addresses three main issues. What voltage- 
dependent channels are present? How are these 
channels regulated by membrane potential, intra- 
cellular calcium, and neurotransmitters? What roles 
do these channels play in cell physiology? Several 
different types of nerve cells are being used: bull- 
frog sympathetic ganglion cells, hippocampal py- 
ramidal cells, lateral geniculate cells, and a clonal 
cell line. 
I. Bullfrog Sympathetic Ganglion. 
M current is a voltage-dependent potassium cur- 
rent that influences firing adaptation in many verte- 
brate neurons and is synaptically regulated. In the 
past year, several issues relating to this current have 
been clarified. FURA imaging has been used to 
show that agents that increase intracellular calcium 
also inhibit M current, suggesting that calcium may 
play a second messenger role. However, experi- 
ments using photolysable calcium buffer show in- 
stead that small increases in intracellular calcium 
actually increase M current. M current increases in 
two other situations: after washout of muscarine 
and after intracellular perfusion with GDP(3S. It is 
unclear if there is any connection between these 
three increases. Only when calcium is increased to 
high levels does M current decrease. This effect re- 
sembles that produced by phorbol esters, in that 
the residual M current becomes muscarine insensi- 
tive. 
Although these experiments complicate possible 
hypotheses about second messengers, other work 
has strengthened the idea that second messengers 
are involved. Cell patch recordings have revealed a 
voltage-dependent potassium channel that gives M- 
like ensemble averages. This putative M channel is 
active in the expected range of membrane poten- 
tials and in a significant fraction of trials is turned 
off by muscarine applied to the rest of the cells but 
not by muscarine in the patch electrode. 
The involvement of intracellular calcium in other 
membrane responses has also been pursued. Con- 
focal microscopy, FLUO imaging, and whole-cell re- 
cording have been combined to examine the dy- 
namics of calcium after a brief activation of 
plasmalemmal calcium channels. Calcium equilib- 
rium throughout the cytoplasm takes —300 ms. 
This is followed by a slowly subsiding, spatially uni- 
form signal. A detailed computer simulation shows 
that this process is accomplished mainly by diffu- 
sion of calcium-loaded buffers. Considerable prog- 
ress has also been made in understanding the ki- 
netics of calcium removal by buffering, uptake into 
intracellular stores, mitochondrial uptake, and ex- 
trusion. 
II. Hippocampal Slices. 
The laboratory has previously identified or clari- 
fied the role of several ionic currents in these cells 
(Ij^, Iq, I^p, and I^^). More recent work has turned 
to transient outward currents previously lumped 
together as l^. It now appears that there are two 
separate 4-aminopyridine-sensitive transient cur- 
rents operating in a similar voltage range. The fast- 
est is a true A current, while the lower one, 1^, is re- 
sponsible for the delayed firing that is seen after 
weak stimuli at hyperpolarized membrane poten- 
tials. 
III. Lateral Geniculate Nucleus (LGN). 
Initial work in rodent LGN characterized tran- 
sient voltage-dependent currents underlying cell 
firing in relay cells. Work has now shifted to feline 
LGN, where different classes of relay cell can be 
readily distinguished. Experiments are being per- 
formed to analyze the contributions of NMDA chan- 
nels and T channels to optic tract evoked synaptic 
potentials. 
IV PCI 2 Cells. 
Efforts to identify biochemical pathways control- 
ling ion channels in sympathetic neurons have 
been hampered by unsuitability of the tissue. To 
overcome this problem work. Dr. Adams and his 
colleagues have initiated work with a chromaffm 
cell line that differentiates to form neuron-like 
cells. These cells possess M current, which is cou- 
pled to activation of bradykinin receptors. 
Dr. Adams is also Professor of Neurobiology and 
Behavior at the State University of New York at 
Stony Brook. 
Continued 
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