Proceedings of The Physiological Society

University of Bristol (2001) J Physiol 536P, S109


The effects of trifluoperazine on the K+ permeability of the isolated frog sciatic nerve perineurium

Barbara A. Todd, M. Karlsson* and W.R. Williams†

School of Health Science, University of Wales Swansea, Singleton Park, Swansea SA2 8PP, * School of Biomedical Sciences, University College of Heath Sciences, S-551 11 Jönköping, Sweden and †Research Unit, School of Care Sciences, University of Glamorgan, Pontypridd CF37 1DL, UK

Trifluoperazine (TFP) is an antipsychotic, anxiolytic drug used in the treatment of psychiatric disorders. It has been shown to exert its effects on several tissues, e.g. calcium permeability is increased in ventricular myocytes (Lefevre et al. 1995), and excitatory postsynaptic potentials are reversibly depressed in the hippocampus CA1 region (Agopyan & Krnjevic, 1993). This study reports the effects of TFP on K+ permeability of the perineurium.

Sciatic nerves were removed from pithed frogs (Rana temporaria) and mounted across a grease-gap chamber for electrical recording of the DC potential and compound action potential (CAP) (Abbott et al. 1990). Changes in the DC potential were used to indicate axonal depolarisation, and the CAP was used as an indication of the health of the axons. The normal protocol consisted of a 10 min stabilising period in Ringer solution, a 2 min pulse of 100 mM K+ Ringer (KCl replacing NaCl), and a further 10 min period in Ringer (control). The nerve was then superfused with 0.5-18 mM TFP (pH 7.2-7.4) for 4-6 min, followed by a 10 min period in Ringer solution, then a repeat pulse of 100 mM K+ Ringer.

In control experiments there was no measurable change in the DC potential or CAP in response to high K+ Ringer. Following the superfusion of the nerve with 0.5-18 mM TFP, Ringer solution, then 100 mM K+ Ringer, there was a dose-dependent change in the DC potential from 1.5-18 mM TFP (range 0.35 ± 0.07 to 5.20 ± 0.23 mV, mean ± S.E.M., n = 44), with a corresponding fall in the amplitude of the CAP. On successive pulses of 100 mM K+ Ringer, changes in the DC potential and CAP amplitude remained constant.

These results demonstrate an irreversible dose-dependent axonal depolarisation of the nerve to TFP, which may be due to disruption of the lipid/protein component of the tight junctions of the perineurium.

M.K. was supported by STINT and B.A.T. by Merck, Sharp & Dohme. We are grateful to Sigma for the donation of trifluoperazine.

    Abbott, N.J., Mitchell, G., Orsmond, P., Todd, B. & Ward, K.J. (1990). J. Physiol. 492.P, 3P.

    Agopyan, N. & Krnjevic, K. (1993). Synapse 13 (1), 10-19.

    Lefevre, T., Coraboeuf, E., Ghazi, A. & Coulobe, A. (1995). J. Membr. Biol. 147 (2), 147-158.

Where applicable, experiments conform with Society ethical requirements