TY - JOUR
T1 - Bretylium-induced voltage-gated sodium current in human lymphocytes
AU - Gáspár, Rezsõ
AU - Krasznai, Zoltán
AU - Márián, Teréz
AU - Trón, Lajos
AU - Recchioni, Rina
AU - Falasca, Marco
AU - Moroni, Fausto
AU - Pieri, Carlo
AU - Damjanovich, Sándor
PY - 1992/10/27
Y1 - 1992/10/27
N2 - 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 μM)-sensitive, and was inhibited by the removal of external Na+ or by the Na+-channel-blocker amiloride (10-44 μM), but K+-channel-blockers 4-aminopyridine (0.1-5 mM) and quinine (100 μM) 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.
AB - 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 μM)-sensitive, and was inhibited by the removal of external Na+ or by the Na+-channel-blocker amiloride (10-44 μM), but K+-channel-blockers 4-aminopyridine (0.1-5 mM) and quinine (100 μM) 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.
KW - (Human lymphocyte)
KW - Bretylium
KW - Ion channel
KW - Patch-clamp
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U2 - 10.1016/0167-4889(92)90195-H
DO - 10.1016/0167-4889(92)90195-H
M3 - Article
C2 - 1329976
AN - SCOPUS:0026768613
VL - 1137
SP - 143
EP - 147
JO - Biochimica et Biophysica Acta - Molecular Cell Research
JF - Biochimica et Biophysica Acta - Molecular Cell Research
SN - 0167-4889
IS - 2
ER -