Cisplatin modulates voltage gated channel currents of dorsal root ganglion neurons of rats

Anke Tomaszewski, Dietrich Busselberg

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

The anticancer drug cis-diammindichloroplatin (CDDP, cisplatin) causes severe side effects like peripheral sensitive neuropathy. The toxicity of CDDP has been linked to changes in intracellular calcium homeostasis ([Ca2+]i). Voltage activated calcium channel currents (ICa(V)) are important for the regulation of [Ca2+]i; therefore, this study was designed to examine the effect of CDDP on ICa(V) in comparison to voltage activated potassium (IK(V)) and sodium (INa(V)) channel currents using the whole cell patch clamp method on dorsal root ganglion neurons of rats. In small neurons (≤Ø20 μm) CDDP reduced peak and sustained ICa(V) concentration dependently (1-100 μM). The IC50 was 23.9 ± 4.5 μM (±S.D.) for the peak current with a Hill-coefficient of 0.6 ± 0.1 and 38.8 ± 6.1 μM for the sustained current (Hill-coefficient: 0.7 ± 0.1). IK(V) were reduced by 20.9 ± 4.8% (10 μM) and INa(V) were only reduced by 9.2% ± 7.2% (10 μM). ICa(V) of large neurons (≥Ø25 μm) were less sensitive to CDDP. The peak ICa(V) was reduced by 14.1 ± 2.3% and IK(V) by 12.8 ± 3.4% (100 μM). The sensitivity of INa(V) in large neurons to CDDP was not different compared to small neurons. We conclude that the reduction of ICa(V) in small cells may be responsible for the neurotoxic side effects CDDP causes in sensory neurons.

Original languageEnglish
Pages (from-to)49-58
Number of pages10
JournalNeuroToxicology
Volume28
Issue number1
DOIs
Publication statusPublished - Jan 2007
Externally publishedYes

Fingerprint

Spinal Ganglia
Cisplatin
Neurons
Rats
Electric potential
Peripheral Nervous System Diseases
Sensory Receptor Cells
Calcium Channels
Clamping devices
Inhibitory Concentration 50
Potassium
Homeostasis
Sodium
Toxicity
Calcium
Pharmaceutical Preparations

Keywords

  • Anticancer drug
  • Cisplatin
  • Dorsal root ganglion neurons
  • Voltage gated calcium currents
  • Voltage gated potassium currents
  • Voltage gated sodium currents

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

Cite this

Cisplatin modulates voltage gated channel currents of dorsal root ganglion neurons of rats. / Tomaszewski, Anke; Busselberg, Dietrich.

In: NeuroToxicology, Vol. 28, No. 1, 01.2007, p. 49-58.

Research output: Contribution to journalArticle

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abstract = "The anticancer drug cis-diammindichloroplatin (CDDP, cisplatin) causes severe side effects like peripheral sensitive neuropathy. The toxicity of CDDP has been linked to changes in intracellular calcium homeostasis ([Ca2+]i). Voltage activated calcium channel currents (ICa(V)) are important for the regulation of [Ca2+]i; therefore, this study was designed to examine the effect of CDDP on ICa(V) in comparison to voltage activated potassium (IK(V)) and sodium (INa(V)) channel currents using the whole cell patch clamp method on dorsal root ganglion neurons of rats. In small neurons (≤{\O}20 μm) CDDP reduced peak and sustained ICa(V) concentration dependently (1-100 μM). The IC50 was 23.9 ± 4.5 μM (±S.D.) for the peak current with a Hill-coefficient of 0.6 ± 0.1 and 38.8 ± 6.1 μM for the sustained current (Hill-coefficient: 0.7 ± 0.1). IK(V) were reduced by 20.9 ± 4.8{\%} (10 μM) and INa(V) were only reduced by 9.2{\%} ± 7.2{\%} (10 μM). ICa(V) of large neurons (≥{\O}25 μm) were less sensitive to CDDP. The peak ICa(V) was reduced by 14.1 ± 2.3{\%} and IK(V) by 12.8 ± 3.4{\%} (100 μM). The sensitivity of INa(V) in large neurons to CDDP was not different compared to small neurons. We conclude that the reduction of ICa(V) in small cells may be responsible for the neurotoxic side effects CDDP causes in sensory neurons.",
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