Ion Channels and Disease: Channelopathies

It seems to me the book might well be read in the context of two other important books in this field: One is Bertil Hille's classic, "Ionic Channels of Excitable Membranes." As a science gathers momentum (and this one is certainly surging) we tend to lose track of what is known and what is simply assumed. Hille's book will fill in some blanks at the fundamental level - and show you exactly where the underlying assumptions are in this science. If you are at all skeptical, and of course you should be, you will like Hille's calm precision and care.

The other background book is Spikes, by Rieke et al. The implication of Spikes is that Adrian was wrong and that, therefore, all of us have been wrong about what nerves actually do - and wrong since 1926. The authors put this rather more diplomatically than I have, but there it is: Adrian wrong.

Spikes summarize evidence accumulated since about 1993 that a single nerve impulse, all by itself, can somehow convey information to the brain. This shocking news will have to be either explained or explained away in terms of the biochemical machinery of the neuron. The current explanation (which is based on precise arrival timing) would seem to rely upon the physiological equivalent of a quartz crystal, um, a device we don't often come across in biochemistry.

It would be my guess that a better understanding of ion channels will point to a more biologically realistic solution. And a new and better picture of how the neuron works.

Ion Channels and Disease is the most current and broadest survey of the subject. The key to the problem is probably in here somewhere, or is referenced here, and is waiting to be discovered. I would pay particular attention to any type of evidence for linkage, structure or signaling between "individual" channels. Linkage between discrete trans-membrane ion channels could create a longitudinal channel running the length of the nerve, probably many of them. A multi-channel axon - a cable rather than a wire -- would be one possible solution to the new mystery of how a single impulse can be freighted with graded information.

Blanche Schwappach, Howard Hughes Medical Institute, University of California, San Francisco