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k in son ' s d i sease in va r ious hydro- g raph ic r eg ions in Q u e b e c pro- vince. T h e y found a remark- able corre la t ion b e t w e e n the two (Spea rman-Rank coeff ic ient 0.967). Whi l e they e m p h a s i z e that the i r data does no t p rove a cause- and-effec t re la t ionsh ip , the i r re- suits are cer ta in ly in t r igu ing . They also d e m o n s t r a t e d s igni f icant ly h i g h e r d i f ferences in hepa t ic cyto- c h r o m e P450 hydroxy la t ion in pa t ien ts w i t h Pa rk inson ' s d isease and sugges t that th is is compat - ible w i t h the i r genera l hypo thes i s that Pa rk inson ' s d i sease is due to a c o m b i n a t i o n of genet ic suscep- t ib i l i ty and an e n v i r o n m e n t a l toxin.

[] [] []

In s u m m a r y , even at this early s tage in the evo lu t ion of our k n o w l e d g e r ega rd ing the mechan - i sm of act ion of MPTP and its metabol i tes , s tud ies of th is com- p o u n d have b r o u g h t us some fasc ina t ing and unexpec t ed ob- servat ions . At the ve ry least, we are a lmos t cer ta in to learn some- t h ing n e w abou t the neu rons of the subs tan t i a n ig ra and the i r funct ion . At the ve ry most , we could h a v e in ou r possess ion a key that wi l l he lp to un lock some of the mys te r i e s of Pa rk inson ' s d i s - e a s e .

R e f e r e n c e s

1 Langston, J. W., Ballard, P., Tetrud, J.W. and Irwin, I. (1983) Science 219, 979--980

2 Davis, G. C., Williams, A. C., Markey, S.P., Ebert, M.H., Caine, E.D., Reichert, C. M. and Kopin, 1. J. (1979) Psychiatr. Res. 1, 249-254

3 Ballard, P. A., Tetrud, J.W. and Langston, J.W. (1985) Neurology 35, 949-956

4 Bums, R. S., Chiueh, C.C., Markey, S.P., Ebert, M.H., Jacobowitz, D.M. and Kopin, I.J. (1983) Proc. Natl Acad. Sci. USA 80, 4546-4550

5 Langston, J. W., Fomo, L.S., Rebert, C. S. and Irwin, I. (1984) Brain Res. 292, 390-394

6 Langston, J. W., Irwin, I., Langston, E.B. and Forno, L.S. (1984) Neurosci. Lett. 48, 87-92

7 Markey, S. P., ]ohannessen, J.N., Chiueh, C.C., Bums, R.S. and Herkenham, M. A. (1984) Nature (Lon- don) 311, 464--467

8 Chiba, K., Trevor, A. and Castagnoli, N. (1984) Biochem. Biophys. Res. Commun. 120, 574-578

9 Langston, J.W., Irwin, I., Langston, E.B. and Fomo, L.S. (1984) Neurosci. Lett. 50, 289-294

10 Singer, T. P., Salach, J. I. and Crabtree, D. (1985) Biochem. Biophys. Res. Com- mun. 127, 707-712

11 Mytilineou, C. and Cohen, G. (1984) Science 225, 529-531

12 Parsons, B. and Rainbow, T. C. (1984) Eur. J. Pharmacol. 102, 375-377

13 Langston, J.W., Irwin, I., Langston, E. B. and Fomo, L. S. (1984) Science 225, 1480-1482

14 Heikkila, R. E., Manzino, L., Cabbat,

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F. S. and Duvoisin, R. C. (1984) Nature (London) 311, 467-469

15 Birkmayer, W., Knoll, J., Riederer, P. and Youdim, M. B. P. (1983) Pharmaco- psychiatry 19, 170-176

16 Chiba, K., Peterson, L. A., Castagnoli, K. P., Trevor, A. J. and Castagnoli, N. Jr. (1985) Drug Metab. Disposition 13, 342- 347

17 Heikkila, R. E., Hess, A. and Duvoisin, R. C. (1985) Life Sci. 36, 231-236

18 Salach, J.I., Singer, T.P., Castagnoli, N. Jr., and Trevor, A. (1984) Biochem. Biophys. Res. Commun. 125, 831~835

19 Fuller, R. W. and Hemrich-Luecke, S. (1985) J. PharmacoL Exp. Ther. 232, 696-701

20 Irwin, I. and Langston, J. W. (1985) Life Sci. 36, 207-212

21 Javitch, J. A. and Synder, S.H. (1984) Eur. J. Pharmacol. 106, 455-456

22 Chiba, K., Trevor, A. J. and Castagnoli, N. Jr., (1985) Biochem. Biophys. Res. Commun. 128, 1228-1232

23 Javitch, J.A., D'Amato, R.J., Strittmatter, S.M. and Snyder, S.H. (1985) Proc. Natl Acad. Sci. USA 82, 2173-2177

24 Ricaurte, G. A., Langston, J.W., DeLanney, L. E., Irwin, I. and Brooks, J. D Neurosci. Lett (in press)

25 Mytilineou, C. and Cohen, J. J. Neuro- chem. (in press)

26 Barbeau, A., Roy, M., Cloutier, T., Plasse, L. and Paris, F. Adv. Neurol. (in press)

27 Ricaurte, G. A., Langston, J. W., Irwin, I., Delaney, L. E. and Fomo, L. S. (1985) Soc. Neurosci. Abstr. P636

28 Jarvis, M. P. and Wagner, G. C. (1985) Neuropharmacology 24, 581-583

29 Sershen, H., Mason, M. F., Hashim, A. and Lajtha, A. (1985) Eur. J. Pharmacol. 113, 135-136

The pros and cons of voltage and patch clamping Voltage and Patch Clamping wi th Microelectrodes

edited by Thomas G. Smi th Jr, Harold Lecar, S teven J. Redman and Peter W. Gage, American Physiological Soci- ety, 1985. US$40.00 I S B N 0683 07773 2

This mul t i - au thored text is the ou tcome of a 1983 workshop on voltage c l amping wi th microelec- trodes. The a im of the editors was to p rov ide graduate s tudents and postdoctoral workers in electrophy- s iology wi th a comprehens ive treat- m e n t of the var ious me thods and pitfalls of voltage c lamping excit- able cells. This a im has been

achieved, bu t perhaps for a more l imi ted audience than the preface suggests. The book is not an easy in t roductory text to the electronics and m e t h o d s r equ i red for the first stages of recording intracellular electrical potentials. The circuit analyses presen ted and mathemat i - cal me thods used are likely to be b e y o n d the scope of the fresh graduate in biological sciences. Howeve r , the physics or electronics graduate m o v i n g into b io logy or the researcher w i th some prev ious exper ience of microelectrode work will f ind a great deal of useful in format ion here.

Three chapters by combina t ions of Finkel, R e d m a n and Gage pro- v ide a quant i ta t ive analysis of voltage c lamping small, spherical cells wi th e i ther two microelec- t rodes or w i th a single electrode

which switches be tween voltage sens ing and current pass ing modes. The advantages and disad- vantages of each approach are lucidly discussed. Those w h o opt for the two electrode clamp will f ind an ent ire chapter by Sachs devo ted to electrode shielding. The c lamping of larger spherical cells is covered by Brown, Wilson and Tsuda in their d iscuss ion of the suct ion pipet te method . Kass and Bennett g ive practical advice on tackling a prepara t ion in which the main tenance of a good space clamp is a p rob lem - in this case the cardiac Purkinje fibre. The prob- lems posed by cellular geomet ry are also considered in chapters by Rall and Segev and Lecar and Smith. Auerbach and Sachs and Lecar and Smi th each discuss the patch clamp method , the former main ly in terms of single channel recording from isolated patches and the latter main ly as an addit ional , and super- ior, means of voltage c lamping small isolated cells. I found the

TIPS - S e p t e m b e r 1985

chapter by Moore on the sucrose gap method to be a somewhat unnecessary addition.

Much emphasis is placed throughout the volume on the technical limitations in damping which are inevitably imposed by any given preparation. The implied message is that time spent initially

in choosing the best preparation may be amply returned in ease of clamping. The material is usually presented clearly, with only iso- lated cases of ambiguous or mis- leading statements (e.g.p.221: hy- perpolarizing the squid axon does not activate sodium channels). Workers thinking seriously of volt-

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age damping a new preparation should certainly find this a useful book.

JIM ELLIOTT

The author is at the Department of Physiology, The University, Dundee DD1 4HN, UK.