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book reviews

NATURE CELL BIOLOGY VOL 2 SEPTEMBER 2000 http://cellbio.nature.com E169

Opening the gates tomolecular medicine

In this age of constantly updated web pagesrelating the latest breakthroughs in bio-medical research, who would attempt to

write not just a review article but a wholebook on a specialized area like ‘chan-nelopathies’? Frances Ashcroft from theUniversity Laboratory of Physiology atOxford did, and her colleagues in relatedfields, as well as advanced students interest-ed in molecular medicine, are very fortunatethat she embarked on this project. The term‘channelopathies’, as defined by the author,"describes those human and animal diseasesthat result from defects in ion channel func-tion". Like any problem in molecular medi-cine, understanding channelopathiesrequires an approach that integrates severallayers of biological complexity — from genesequence to protein function to cellular reg-ulation to organ physiology. The recentexplosion of sequence data available to thescientific community has accelerated certainsteps in the corresponding research so muchthat keeping track has become a challenge.No wonder the author felt "like the RedQueen in Alice in Wonderland, who had torun ever faster in order to remain in thesame place" while writing this book.

But why do ion channels warrant a spe-cial term for such an ostensibly commoncircumstance, in which malfunction of aprotein can lead to disease? What specialcontribution does the ion channel fieldadd to the general endeavour of molecularmedicine? Searching OMIM, the cata-logue of genetically linked diseases acces-sible via the website of the NationalCenter for Biotechnology Information(http://www.ncbi.nlm.nih.gov.) tells usthat it is not numbers. Although thesearch term ‘channel*’ yields an impres-sive number of entries (388, not necessar-ily all channelopathies), so do ‘protease*’(314), ‘kinase*’ (1,143) and ‘transcriptionfactor*’ (1,019). The answer may have twoparts and is related to traversing the levels ofbiological complexity mentioned before.First, the function of ion channels can bestudied to a level of quantitative precision

that is often hard to achieve for other pro-teins. This can be crucial to understandingthe link between protein function and cel-lular processes, particularly in the moreinteresting cases of disease caused byaltered protein function (rather than lossof protein function). Second, ion channelsare central to an astounding number ofphysiological processes, such as nerve andmuscle excitation, epithelial transport, andhormone secretion, to name but a few. Asthe book illustrates, there are many chan-nelopathies in which the molecular defectcan be satisfactorily linked to a complexphysiological outcome — textbook exam-ples of molecular medicine. These includediseases of blood-pressure regulationcaused by mutations in the genes encodingsubunits of the epithelial sodium channel,and neurological disorders like startle dis-ease, which is caused by mutations in thegene for a subunit of the glycine-receptorion channel. Another notable example isthe inherited cardiac disorder long QT syn-drome, which can be caused by mutationsin at least four different ion channel genes.

The book is self-contained in the sensethat it provides all the background knowl-edge necessary to understand the field(three chapters and brief interludes). Theauthor’s attention to outlining methodolo-gy should be particularly useful to students,as this aspect of how to ask scientific ques-tions is not always taught early enough. Thetwenty main chapters are devoted to partic-ular families of cloned ion channels. Ourknowledge about these groups of channelsas well as their apparent medical relevancevaries vastly. Ashcroft, however, has turnedthis variation around and uses it to makethe chapters less uniform. All the impor-tant information is there, yet the book is inno sense a catalogue (precisely the reasonthat it makes sense as a book rather than aninternet page). It manages to communicatecomplex ideas with clarity, precision andefficiency, and I personally enjoyed thesense of history that pervades the book, aswell as the lucid style in which it is written.

It is almost ironic that, in the face ofsuch successful integration of different lev-els of biological complexity, the middleground is somewhat blurry. From the pointof cell biology there are wide gaps in ourunderstanding of how ion channels areintegrated into cellular pathways and regu-lative networks. This applies particularly toion channels that are localized to the mem-branes of intracellular organelles. Ofcourse, the book cannot reflect this situa-tion, as the author herself recognises in theconcluding remark —

"‘Well, in our country,’ said Alice, stillpanting a little, ‘you’d generally get to some-where else if you ran very fast for a longtime as we’ve been doing.’ ‘A slow sort ofcountry!’ said the Queen. ‘Now, here, yousee, it takes all the running you can do, tokeep in the same place. If you want to getsomewhere else, you must run at least twiceas fast as that!’." Thanks to the headstartAshcroft provides, the reader should be ableto live up to the challenge and ‘run twice asfast’ to tackle some of the exciting questionsraised by Channelopathies.Blanche Schwappach is at the ZMBH,Universitate Heidelberg, Im Neuenheimer Feld282, D-69120, Heidelberg, Germany.e-mail: b.schwappach@zmbh.uni-heidelberg.de

Ion Channels and Disease —Channelopathies by Frances Ashcroft

Academic Press · October 1999Hardback £46.95/$75

Blanche Schwappach

Launch of book section

In August 2000, Nature Cell Biologylaunched this new section to provide aforum for the scholarly assessment of newlypublished books. This section will appearevery month and will feature lively, criticalreviews covering a broad spectrum of titlesranging from protocols, to in-depth reviewsof specific topics, to biographies.

We hope this section will be informativein guiding our readers’ decisions whether tobuy a particular book, whilst giving themore casual reader an opportunity tobecome familiar with the state of the fieldcovered by these publications.