title: A voltage dependent non-inactivating Na+ channel activated during apoptosis in Xenopus oocytes.
abstract: Ion channels in the plasma membrane are important for the apoptotic process. Different types of voltage-gated ion channels are up-regulated early in the apoptotic process and block of these channels prevents or delays apoptosis. In the present investigation we examined whether ion channels are up-regulated in oocytes from the frog Xenopus laevis during apoptosis. The two-electrode voltage-clamp technique was used to record endogenous ion currents in the oocytes. During staurosporine-induced apoptosis a voltage-dependent Na(+) current increased three-fold. This current was activated at voltages more positive than 0 mV (midpoint of the open-probability curve was +55 mV) and showed almost no sign of inactivation during a 1-s pulse. The current was resistant to the Na(+)-channel blockers tetrodotoxin (1 µM) and amiloride (10 µM), while the Ca(2+)-channel blocker verapamil (50 µM) in the bath solution completely blocked the current. The intracellular Na(+) concentration increased in staurosporine-treated oocytes, but could be prevented by replacing extracellular Na(+) with either K(+) or Choline(+). Prevention of this influx of Na(+) also prevented the STS-induced up-regulation of the caspase-3 activity, suggesting that the intracellular Na(+) increase is required to induce apoptosis. Taken together, we have found that a voltage dependent Na(+) channel is up-regulated during apoptosis and that influx of Na(+) is a crucial step in the apoptotic process in Xenopus oocytes.
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Ulrika H
authors.initials: UH
authors.lastname: Englund
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Jens
authors.initials: J
authors.lastname: Gertow
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Katarina
authors.initials: K
authors.lastname: Kågedal
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Elinder
mesh_terms: D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D009865:Oocytes / Q000187:drug effects* / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D026941:Sodium Channel Blockers; D061566:Voltage-Gated Sodium Channels; D013779:Tetrodotoxin; D000584:Amiloride; D014700:Verapamil