Modulatory effect of NO on sodium currents in a neuroblastoma cell line: aspects of cell specificity.
Nitric oxide (NO) participates in the regulation of many cell functions in the CNS, including modulation of ion channel function by direct changes in the channel protein structure, modulating permeability or gating kinetics. The mechanisms by which NO donors modulate sodium currents are protein and tissue specific. The present paper concerns sodium currents in the neuroblastoma N1E-115 cell line, applying whole-cell voltage clamp methods. Sodium currents were characterized in terms of the sensitivity to NO donors and the hydrophilic thiol oxidizer thimerosal. Parameters defining steady-state inactivation and activation, removal of inactivation and the voltage dependence of inactivation, were determined before and after thimerosal application. The results concerning the application of thimerosal showed blockade of the resting state, hyperpolarizing shifts of m(infinity) and h(infinity) curves, change in the voltage sensitivity and slower inactivating kinetics, tau(hf) and tau(hs) being affected in the same manner. The present results provide clear evidence for redox modulation of the sodium channel population in N1E-115 cells. Our results showed that the membrane-permeable alkylating agent (NEM) does not inhibit current reduction determined by thimerosal. We have reasons to suspect that the sodium channel population in N1E-115 cells differs in the proposed consensus sequence for nitrosylation or thimerosal cysteine oxidation.
Ribeiro
Maria Alexandra
MA
Departamento de Fisiologia, Faculdade de Ciências Médicas, U.N.L., Campo Santana 130, 1169-056 Lisboa, Portugal. maribeiro@fcm.unl.pt
Cabral
Henrique Oliveira
HO
Costa
Pedro Freire
PF
D000818:Animals; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D009447:Neuroblastoma / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D011310:Preservatives, Pharmaceutical / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D018709:Statistics, Nonparametric; D013849:Thimerosal / Q000494:pharmacology
D020030:Nitric Oxide Donors; D011310:Preservatives, Pharmaceutical; D015222:Sodium Channels; D013849:Thimerosal; D009569:Nitric Oxide