Molecular Studies of Voltage-Sensitive Potassium Channels 
any experimental organism, as long as it is amena- 
ble to the specific type of experimentation, will 
reveal information of medical interest. 
An intriguing finding is that the Shaker potas- 
sium channel gene in the fruit fly gives rise to a 
number of protein products by alternative splic- 
ing of the primary RNA transcript. These diff'erent 
protein products probably form diff'erent sub- 
types of this potassium channel, because they 
show differential tissue distribution and, when 
expressed in frog oocytes, they give rise to chan- 
nels of different kinetic properties. Alternative 
splicing of the potassium channel gene, together 
with the potential mix and match of subunits 
from one or more genes, offers a possible mecha- 
nism for generating potassium channel diversity. 
Having cloned a potassium channel gene, we 
can now ask how this channel works. How does it 
detect a voltage change across the cell membrane 
and, responding, open? How does it "inactivate" 
after it opens? How does it discriminate between 
sodium and potassium ions and show exquisite 
selectivity? To probe these questions, we have 
altered specific residues of the potassium chan- 
nel to see how the various functions are affected. 
For studies of the biological functions of potas- 
sium channels, we have chosen to concentrate on 
the mammalian heart and hippocampus. A variety 
of cardiac potassium channels have been charac- 
terized biophysically and are important in con- 
trolling the rhythmic heartbeat. Molecular stud- 
ies of these channels not only will contribute to 
our understanding of channel function but also 
will be relevant clinically, for example, in the 
development of more specific drugs for arrhyth- 
mia. The hippocampus is a region of the mamma- 
lian brain that appears to play an important role 
in learning and memory. It has also been studied 
extensively in experimental paradigms that in- 
duce epileptic activity. By cloning and analyzing 
potassium channel genes that are expressed in 
this tissue, we hope to learn about the involve- 
ment of these potassium channels in the normal 
function and pathology of the nervous system. 
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