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Perspectives
The
Unexpected Vista - by Fred Sigworth
In science
one comes from time to time upon a vista, a place where with the sight
of imagination or sometimes with direct observation a new landscape
opens up before the eyes. Being a scientist brings with it the privilege
of being the one to see some of these vistas for the first time. Being
in the academic community of the university also means that one has
comrades who can understand and share the excitement-since science is
a community effort that involves both discovery and the sharing of knowledge.
As a psalm summarizes it, "One generation shall declare Thy works to
another."
In the
latter 1970s, when I was a graduate student at Yale, the concept of
ion channels as discrete protein molecules was just becoming clear.
It was known for example what the total sodium conductance of a cell
membrane was, but we did not know how many sodium channels operated
to control this permeability. My advisor gave me considerable freedom,
basically turning me loose in his laboratory to try out my new approach
to estimate the single-channel conductance. The approach worked, resulting
in an estimate for the number of picosiemens of conductance per channel,
and resulting in a PhD thesis. The experiments also gave evidence that
the way the channels regulate their conductance is by the rapid, random
switching between "on" and "off" states. The evidence was indirect-it
involved the statistics of fluctuations in the sodium current-but it
was convincing to me, and to those people who understood the theory
involved.
One evening
two years later I was riding home on my bicycle, full of wonder at a
new experiment just completed, in which I had seen on an oscilloscope
screen the individual square pulses of current from sodium channels
for the first time. It is maybe not for everyone to be so excited that
one can "see" the workings of one ion channel on an oscilloscope screen,
but for me and some of my colleagues, it was an event that we had looked
forward to for some time. The "vista" opened up by this single-channel
recording was better than what I had imagined.
Perhaps
you have learned about something that has you intrigued. Maybe you feel
the motivation of wanting to understand, to see a biological process
more clearly. You would like to read about what is known, and spend
time contriving experimental ways to see it better. This is the kind
of motivation I have felt. In my case, I first heard about ion channels
as an undergraduate student in applied physics, and was intrigued by
the idea that protein molecules could act as devices like transistors,
switching electric currents in response to voltage changes. The mechanism
by which channel proteins do this has turned out to be a remarkable
one, and one that I would still like to see more clearly.
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