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.