Voltage-dependent slowly activating anion current regulated by temperature and extracellular pH in mouse B cells

Abstract

Voltage-dependent, outwardly rectifying anion channels have been described in various cells including lymphocytes. In this study, we found that murine B cells express the voltage-dependent slowly activating anion channels (VSACs). Using a whole-cell configuration, IVSAC in Bal-17 was induced by a sustained depolarization (>0 mV) which was remarkably facilitated at 35°C (Q10=23 at 30 mV of clamp voltage). Substitution of extracellular Cl- with gluconate shifted the reversal potential to the right (35.7 mV). Gd3+ (IC50=0.11 μM) significantly attenuated IVSAC, but DIDS partially blocked IVSAC. In addition, extracellular acidification suppressed IVSAC whereas alkalinization facilitated the channel activation. IVSAC was decreased by 90% at pH 6.35 and increased by 180% at pH 8.0. In cell-attached and inside-out patch clamps, depolarization slowly activated the anion channels of large conductance (∼270 pS) with multiple levels of subconductances. The single channel currents were also blocked by Gd3+ and acidic pH. Furthermore, I VSAC was also observed in WEHI-231 (an immature B cell line) and freshly isolated splenic B cells of mice. In summary, murine B cells express unique voltage-dependent anion channels that show a strong sensitivity to both temperature and extracellular pH. Further investigation is required to understand the physiological roles of VSAC and its molecular identity. © Springer-Verlag 2006.