Effects of inorganic and triethyl lead and inorganic mercury on the voltage activated calcium channel of Aplysia neurons.

Using conventional two electrode voltage clamp techniques we have studied the effects of Pb2+, triethyl lead (TEL) and Hg2+ on voltage-activated calcium channels of Aplysia neurons and found that all three metals are potent inhibitors at micromolar concentrations. However, the time course of current reduction or block and its reversibility vary when comparing Pb2+ to TEL and Hg2+. With application of Pb2+ the calcium current decreases immediately and a steady state is reached within three to seven minutes, depending upon the concentration of Pb2+ (IC50 = 61 microM). The block was easily reversed upon wash out of Pb2+ with a time course similar to that of onset. Perfusion with either TEL (5 to 50 microM) or Hg2+ (5 to 200 microM) resulted only in a small reduction of current when the substances reached the cell membrane but with clear reduction within 2 min. The decrease continued at about the same speed for the total duration of the application. Upon washing there was no recovery of the response. At the onset of washing the rate of current decline stopped for several minutes, but then the current continued to decline at a slower rate in the absence of toxicant. Our data suggest that Pb2+ acts by a direct and reversible blockade of the calcium channel. In contrast TEL and Hg2+ act slowly and irreversibly to block calcium channels at concentrations which do not greatly affect membrane potential or resistance. In spite of the slow time course these substances are probably acting directly on the calcium channel.