title: Bretylium-induced voltage-gated sodium current in human lymphocytes.
abstract: Using the whole-cell variation of the patch-clamp technique it has been determined that 0.25-3 mM bretylium tosylate (BT) exerts a repolarizing effect on partially depolarized human lymphocytes. The repolarizing effect was ouabain (40 microM)-sensitive, and was inhibited by the removal of external Na+ or by the Na(+)-channel-blocker amiloride (10-44 microM), but K(+)-channel-blockers 4-aminopyridine (0.1-5 mM) and quinine (100 microM) had no effect. The drug induced a sodium dependent, amiloride-sensitive transient inward current reaching its maximum value approx. 20-30 s after the administration of BT and lasting for 6-10 min. This current was activated by depolarization within 25 ms at around -42 mV, its inactivation took about 2 s and its reversal potential was +24 +/- 5 mV. An increase in the intracellular sodium concentration (1.8-3.2 mM) has been observed upon the addition of BT by monitoring the SBFI fluorescence of the dye-loaded cells. It has been shown that whole-cell K+ currents are significantly decreased by BT. The existence of voltage and ligand (BT)-gated sodium channels has been postulated in human lymphocytes. These channels are thought to participate in the initiation of membrane repolarization in human lymphocytes, and thereby influence mitogenic or antigen-induced cell-activation processes.
authors.affiliation: Department of Biophysics, University Medical School of Debrecen, Hungary.
authors.forename: R
authors.initials: R
authors.lastname: Gáspár
authors.forename: Z
authors.initials: Z
authors.lastname: Krasznai
authors.forename: T
authors.initials: T
authors.lastname: Márián
authors.forename: L
authors.initials: L
authors.lastname: Trón
authors.forename: R
authors.initials: R
authors.lastname: Recchioni
authors.forename: M
authors.initials: M
authors.lastname: Falasca
authors.forename: F
authors.initials: F
authors.lastname: Moroni
authors.forename: C
authors.initials: C
authors.lastname: Pieri
authors.forename: S
authors.initials: S
authors.lastname: Damjanovich
mesh_terms: D001949:Bretylium Compounds / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*
chemical_list: D001949:Bretylium Compounds; D015222:Sodium Channels; C045166:bretylium