Actions of cisplatin on the electrophysiological properties of cultured dorsal root ganglion neurones from neonatal rats.
In this study we have employed the whole cell patch clamp technique to investigate the effects of an anti-cancer drug cisplatin on basic electrophysiological properties of cultured dorsal root ganglion neurones from neonatal rats. The results show that within the clinical concentration range, cisplatin (0.1 to 10 microM) caused a decrease in input conductance, and complex changes in resting membrane potential in these cultured sensory neurones. The dominant effects of cisplatin on input conductance may be due to inhibition of leak conductances. Transplatin (5 microM) was significantly less effective than cisplatin at reducing input conductance which suggests a degree of stereoselectivity. Cisplatin (1 to 5 microM) transiently increased excitability of the cultured neurones as reflected by a reduction in the threshold for activation of action potentials by 8 mV. The rise time, peak amplitude and duration of action potentials were not changed by acute application of 5 microM cisplatin. Long term treatment of neurones with cisplatin (5 microM), for up to 1 week reduced the viability of the cultures, and attenuated neurone excitability, although input conductance of the cells was significantly increased to 322 +/- 49 M omega (n = 9) compared with controls of 210 +/- 20 M omega (n = 30; P < 0.05). Acute and chronic treatment of cultured neurones with cisplatin therefore produced contrasting actions.
Scott
R H
RH
Department of Physiology, St. George's Hospital Medical School, London, UK.
Manikon
M I
MI
Andrews
P L
PL
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology*; D004334:Drug Administration Schedule; D004594:Electrophysiology; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects*; D005731:Ganglionic Stimulants / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism
D005731:Ganglionic Stimulants; C034697:transplatin; D002945:Cisplatin