Blocking effects of cobalt and related ions on the gamma-aminobutyric acid-induced current in turtle retinal cones.

Red-sensitive cone photoreceptors were isolated from the turtle retina, and GABA-induced currents were recorded under voltage clamp. The effect of Co2+, widely used as a blocker of chemical synapses, on the GABA-induced current was studied. Co2+ blocked the GABA-induced current evoked by local application either at the synaptic region (cone pedicle) or at the extra-synaptic region (cell body). 5 microM-Co2+ suppressed the GABA-induced current by 50%, and a few hundred microM-Co2+ blocked it almost completely. Co2+ suppressed the GABA-induced current non-competitively: the saturating response amplitude decreased without a change in the threshold or saturating dose of GABA. The blocking was not voltage dependent in the physiological range of the membrane potential. Ni2+ and Cd2+ also blocked the GABA-induced current non-competitively, and were as effective as Co2+. Tetraethylammonium (25 mM) showed a similar but weaker blocking effect. On the other hand, Mg2+ (20 mM), Mn2+, Sr2+, Ba2+ (10-100 microM each), D-600 (10 microM) or Cs+ (10 mM) did not affect the GABA-induced current. The Ca current in the turtle cones was blocked almost completely by 20 mM-Mg2+ or 4 mM-Co2+, or strongly suppressed by 10 microM-D-600. However, Cd2+ and Ni2+ (10 microM each) blocked the Ca current by ca. 50%, and Co2+ and Mn2+ (10 microM each) suppressed it only partially. The blocking of the GABA-induced current by these agents was, therefore, not directly related to the blocking of the Ca current and/or Ca-mediated currents. These observations present a warning on the use of some divalent cations, such as Co2+, Ni2+ or Cd2+, as a presynaptic blocker at the GABAergic synapse. High concentrations of Mg2+ are recommended as a more appropriate blocker.