SnCl(2) reduces voltage-activated calcium channel currents of dorsal root ganglion neurons of rats.
Stannous dichloride (SnCl(2)) occurs in the environment where it has been especially enriched in aquatic ecosystems. Furthermore, it is used in food manufacturing (e.g. for stabilizing soft drinks or as an anti-corrosive substance) and in nuclear medicine where it is employed as a reducing agent for technecium-99m (99mTc) and therefore is applied intravenously to human beings. SnCl(2) is known to have toxic effects on the nervous system which can be related to alterations of intracellular calcium homeostasis ([Ca(2+)](i)). In this study the whole cell patch clamp technique is used on dorsal root ganglion neurons of 3-week-old "Wistar" rats to evaluate the effects of SnCl(2) on voltage-activated calcium channel currents (I(Ca(V))). I(Ca(V)) were reduced concentration-dependently by SnCl(2) (1-50microM). 1microM SnCl(2) reduced I(Ca(V)) by 8.1+/-4.5% (peak current) and 19.2+/-8.9% (sustained current), whereas 50microM inhibited I(Ca(V)) by 50.6+/-4.3% (peak current) and 55.6+/-11.3% (sustained current). Sustained currents were slightly but not significantly more reduced than peak currents. The effect appeared not to be reversible. The threshold concentration was below 1microM. The current-voltage relation did not shift which is an indication that different calcium channel subtypes were equally affected. There was a slight but not significant shift of the activation/inactivation curves towards the depolarizing direction. We conclude that voltage-gated calcium channels are affected by Sn(2+) similarly to other divalent metal cations (e.g. Pb(2+) or Zn(2+)). The reduction of I(Ca(V)) could be related to the neurotoxic effects of SnCl(2).
Tomaszewski
Anke
A
Institut für Physiologie, Universitätsklinikum Essen, Universität Duisburg-Essen, Hufelandstrasse 55, 45122 Essen, Germany.
Büsselberg
Dietrich
D
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005727:Ganglia, Spinal / Q000166:cytology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques / Q000379:methods; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism*; D051381:Rats; D017971:Tin Compounds / Q000494:pharmacology*
D024642:Potassium Channels, Voltage-Gated; D017971:Tin Compounds; C023599:stannous chloride