Block of sodium currents by the calcium antagonist D600 in human heart cell segments

Abstract

The effects of micromolar concentrations of racemic D600 on the transmembrane inward sodium current (I_Na) were investigated in voltage clamped, intracellularly perfused, human heart cell segments. Extracellular D600 blocked I_Na in a ‘voltage- and ratedependent’ manner as shown by the enhanced I_Na depression with a reduction of the ‘resting’ transmembrane polarization (Vm) and stimulation interval (SI). D600 action was manifested as a voltage-dependent slowing down of the Na⁺ channels' recovery kinetics after a pulsed excitation, with greater recovery times during longer depolarized states, excited or non-excited. This phenomenon seems linked to the improved control of the intracellular environment normally influencing channel activity, and to the increased ratio of ‘non-sarcolemmal’ to ‘sarcolemmal’ cell membranes for this preparation.