Molecular Studies of Voltage-Sensitive Potassium Channels 
IsacofF, George Lopez, Diane Papazian, and Leslie 
Timpe; this work is supported by a grant from the 
National Institutes of Health) and others have 
provided evidence for the involvement of spe- 
cific structural elements in the detection of volt- 
age changes across the cell membrane and in the 
subsequent conformational changes that open 
the channel and allow the cytoplasmic mouth of 
the pore to interact with the inactivation gate, 
thereby terminating channel opening. 
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 will not only contribute to 
our understanding of channel function but will 
also be relevant clinically, for example, in the 
development of more-specific drugs for cardiac 
arrhythmia. The hippocampus is a region of the 
mammalian brain that appears to play an impor- 
tant role in learning and memory. It has also been 
studied extensively in experimental paradigms 
that induce epileptic activity. By cloning and ana- 
lyzing potassium channel genes that are ex- 
pressed in this tissue, we hope to learn about the 
involvement of these potassium channels in the 
normal function and pathology of the nervous 
system. 
Using specific probes for individual potassium 
channel polypeptides and their messenger RNA, 
Morgan Sheng and Meei-ling Tsaur have found 
distinct patterns of expression in the mammalian 
brain. In addition to spatial regulation at the level 
of brain regions as well as specific neuronal 
types, dynamic changes in potassium channel 
gene expression have also been observed in 
the adult brain following pentylenetetrazole- 
induced seizure. (This work is supported by a 
grant from the National Institute of Mental 
Health.) The observed decrease of specific potas- 
sium channel transcripts in the excitatory neu- 
rons in the dentate gyrus of the hippocampus is 
likely to lead to an increase of excitability. These 
observations suggest that potassium channel gene 
regulation may contribute to long-term neuronal 
plasticity. 
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