VOLTAGE-GATED CALCIUM-CHANNEL CURRENTS OF RAT DORSAL-ROOT GANGLION (DRG) CELLS ARE BLOCKED BY AL3+

The effects of the trivalent cation aluminum (Al3+) on voltage activated calcium channel currents were examined. Al3+ blocks sustained and transient components of voltage activated calcium channel currents of cultured rat dorsal root ganglion (DRG) cells. Currents were elicited by voltage jumps from -80 to 0 mV. The channel block was use dependent. Steady state blockade occurred after 1 to 5 min, when opening the channel every 10 s. There was little or no recovery after washing. Threshold concentration was about 20 muM Al3+ and total blockade (> 80%) was obtained at 200 muM Al3+; the IC50 was 83 muM and the Hill number was around 3. The degree of blockade was pH dependent, and increased with H+ concentration. The current-voltage relation frequently shifted to depolarised voltages after applying Al3+. The degree of the shift was a function of Al3+ concentration, but the magnitude differed from cell to cell. In the effective concentration range (< 200 muM Al3+) the effect was quite specific to voltage activated calcium channel currents. Voltage activated potassium and sodium channels were reduced less than 15% by 200 muM Al3+. We conclude that Al3+ is a potent and irreversible blocker of voltage activated calcium channel currents in mammalian neurons.