Bretylium-induced voltage-gated sodium current in human lymphocytes.
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.
Gáspár
R
R
Department of Biophysics, University Medical School of Debrecen, Hungary.
Krasznai
Z
Z
Márián
T
T
Trón
L
L
Recchioni
R
R
Falasca
M
M
Moroni
F
F
Pieri
C
C
Damjanovich
S
S
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*
D001949:Bretylium Compounds; D015222:Sodium Channels; C045166:bretylium