Insensitivity of the open state of (-)-DPI-modified cardiac Na+ channels to the blocking effects of the (+) enantiomer

Abstract

Elementary Na+ currents in DPI-modified cardiac Na+ channels were recorded in the absence and presence of the blocking (+) enantiomer in inside-out patches from cultured neonatal rat cardiocytes. After external application of (-)-DPI (3 mumols/l), the kinetics of modified, non-inactivating Na+ channels were found to be indistinguishable from the channel kinetics observed in the presence of (+/-)-DPI (6 mumols/l). The open state and burst duration proved insensitive to the blocking (+) enantiomer in concentrations up to 3 mumols/l. At -30 mV, the exit rates from the open and the bursting state were 105 +/- 11 and 57 +/- 6 s-1, respectively, with (-)-DPI or 88 +/- 6 and 49 +/- 8 s-1, respectively, with (+/-)-DPI. The use of (+/-)-DPI 201-106 as a pharmacological modifier of channels will, therefore, provide reliable kinetic data of non-inactivating Na+ channels.