Retinoic acid inhibits Ca2+ currents and cell proliferation in a B-lymphocyte cell line

Using the whole-cell variation of the patch-clamp technique, we have demonstrated that retinoic acid (RA) blocks Ca channels and inhibits cell proliferation in a mouse hybridoma cell line (MHY206) derived from a fusion of murine myeloma and splenic B cells. In 25 mM external Ca, and with an Na internal solution containing aspartate, cAMP, and Mg-ATP, inward currents were activated in these cells from holding potentials more negative than -70 mV, peaked at voltage steps up to -20 mV, and were voltage-inactivated within the 125-msec duration of the pulse. With more positive pulses, outward current carried by Na ions permeating through the Ca channels were seen. Application of RA blocked both inward and outward current through the Ca channels in a dose-dependent manner, with 50% block at a concentration of around 5 x 10(-5) M. Proliferation was blocked by 75% at that concentration, and the same relation between the reduction in current and proliferation was seen throughout the concentration range. A similar reduction of Ca currents and proliferation was demonstrated with octanol, a long-chain alcohol that has recently been reported to block Ca channels. These results suggest a role for Ca channels in the proliferation of MHY206 cells and implicate blockage of these channels as contributing to the antiproliferative activity of RA.