Mechanically Activated Ion Channels 
seems more like an active, force-producing mo- 
tor than a relaxation. 
Further evidence from our laboratory suggests 
that the "motor molecule" that moves the attach- 
ment point is like myosin, the protein that causes 
muscle to contract, and we are now seeking to 
coniirm or refute this analogy. 
Our ultimate aim is to describe each link in the 
mechanical chain from cilia to channels, in terms 
of the protein identity of the links, their biophysi- 
cal properties, and their relationship to each 
other. Such a description would contribute to the 
long-range goal of a comprehensive theory of me- 
chanically activated channels, not only in the ear 
but in the many other cell types that display a 
mechanical sensitivity. 
The location of our laboratory in a hospital has 
also encouraged collaborative projects related to 
neurological disease. One of the more interesting 
recent projects involves an inherited muscle dis- 
order, hyperkalemic periodic paralysis. This ge- 
netic disease, which causes sporadic weakness or 
paralysis, is dominantly inherited, so that a child 
has a 50-50 chance of being affected. 
Exercise or certain foods, which raise the level 
of blood potassium, can bring on a paralytic at- 
tack. Earlier experiments had indicated that the 
increased potassium can change the resting volt- 
age of the muscle and (perhaps indirectly) acti- 
vate special channels that pass sodium ions. Col- 
laborators at the Massachusetts General Hospital 
showed that the disease is genetically linked to 
the muscle sodium channel gene, implicating 
these channels. We then measured the activity of 
sodium channels in muscle from an affected pa- 
tient and found them defective. The defect ex- 
plains the pathology. Elevated potassium pre- 
vents some of the defective sodium channels 
from closing, and the steady influx of sodium 
changes the voltage so as to open — and then per- 
manently close — all the other channels. The 
muscle then cannot contract, causing paralysis. 
Consistent with dominant inheritance, a small 
fraction of defective channels indirectly inacti- 
vates all the rest, including the normal ones in- 
herited from the other parent. Understanding the 
pathology at the molecular level gives hints for 
effective drug treatment. 
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