it seems likely that adaptation is mediated by 
movement of the tip-link attachments along the 
stereocilia. 
Based on the physiological limits to adaptation, 
however, the expected movement of the densities is 
also limited. In fact, the average movement mea- 
sured from thousands of electron micrographs was 
no more than ~ 50-75 nm, even for very large de- 
flections of the bundles. This is in good agreement 
with the prediction from the physiological limit. 
Still unclear is what sort of microscopic structure is 
responsible. Is it like a fence or a tether? 
Hyperkalemic Periodic Paralysis 
In a related project Dr. Stephen Cannon in Dr. 
Corey's laboratory has been working on the molecu- 
lar basis of an inherited muscle disease, hyperkale- 
mic periodic paralysis (HPP), which causes weak- 
ness or paralysis when serum potassium is raised. 
Last year Dr. James Gusella's laboratory (Massachu- 
setts General Hospital) found that the gene for the 
sodium channel a subunit was coinherited with 
HPP. Dr. Cannon then studied muscle from an af- 
fected patient and found that the sodium channels 
were themselves defective: with high extracellular 
potassium, they occasionally fail to inactivate. 
Still remaining were three important questions: Is 
there a genetic defect in the a subunit? Can such a 
defect account for the inactivation failure observed 
in HPP muscle? Does the inactivation failure fully 
account for the pathology? 
This year several groups were able to identify sin- 
gle nucleotide substitutions in the a subunit from 
patients with HPP. There are different mutations in 
different families, indicating that the disease arises 
spontaneously. Thus defects in the gene coinherit 
with the disease. 
Dr. Cannon then inserted two of these mutations 
into the sodium channel a-subunit gene from the 
rat. As expected, the mutated channels, when ex- 
pressed in a human cell line, demonstrate failure of 
inactivation similar to that seen in muscle from pa- 
tients. Curiously, the mutated rat channel did not 
show the characteristic potassium sensitivity. This 
may have to do with the cell line used for expres- 
sion; it may result from the absence of the 0 subunit; 
or it may be a difference between rat and human 
genes. Thus the genetic defects do produce the phys- 
iological defect. 
Finally, Dr. Cannon mimicked the physiological 
defect with an anemone toxin that also produces 
inactivation failure. Rat muscle treated with toxin to 
produce moderate inactivation failure showed in- 
creased electrical excitability and slower relaxation 
of tension when stimulated, features characteristic 
of the myotonia that often precedes a paralytic at- 
tack in HPP. 
The effects of more inactivation failure were stud- 
ied with a computer model of excitation in muscle. 
This indicated that muscle can behave in three dis- 
tinct manners, depending on the degree of inactiva- 
tion failure: at low levels, excitation is normal and a 
patient would show no symptoms; at intermediate 
levels, hyperexcitability results, producing clinical 
myotonia; at high levels, the muscle is locked up at a 
higher voltage, permitting no excitation, and the pa- 
tient is paralyzed. The physiological defect thus ac- 
counts for the disease. 
Dr. Corey is also Associate Neurobiologist in the 
Department of Neurology at Massachusetts Gen- 
eral Hospital, Boston, and Associate Professor of 
Neuroscience at Harvard Medical School. 
Books and Chapters of Books 
Corey, D.P., and Assad, J.A. 1992. Transduction and 
adaptation in vertebrate hair cells: correlating 
structure with function. In Sensory Transduc- 
tion (Corey, D.P., and Roper, S.D., Eds.). New 
York: Rockefeller University Press, pp 325-342. 
Articles 
Assad, J.A., Shepherd, G.M.G., and Corey, D.P. 
1991. Tip-link integrity and mechanical trans- 
duction in vertebrate hair cells. Neuron 7:985- 
994. 
Pickles, J. O., and Corey, D.P. 1992. Mechanoelec- 
trical transduction by hair cells. Trends Neurosci 
15:254-259. 
Shepherd, G.M.G., and Corey, D.P. 1992. Sensa- 
tional science. Sensory Transduction: 45th An- 
nual Symposium of the Society of General Physiol- 
ogists, Marine Biological Laboratory, Woods Hole, 
MA, USA, September 5-8, 1991. New Biol 4:48- 
52. 
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