Gadolinium block of calcium channels: influence of bicarbonate

The selectivity of block of voltage-activated barium (Ba⁺) currents by lanthanide ions was studied in a rat dorsal root ganglion (DRG) cell line (F11-B9), rat and frog peripheral neurons, and rat cardiac myocytes using the whole-cell patch clamp technique. Gadolinium (Gd³⁺) produced a dose-dependent and complete inhibition of whole-cell Ba²⁺ current in all cells studied, including cells expressing identified dihydropyridine-sensitive L-type currents and ω-conotoxin-sensitive N-type currents. Like Gd³⁺, lutetium (Lu³⁺) and lanthanum (La³⁺) blocked all Ba²⁺ current with little selectivity for different components of the whole-cell current. Gd³⁺ block of Ba²⁺ currents was incomplete, however, when sodium bicarbonate (5–22.6 mM) was added to the standard HEPES-buffered external Ba⁺ solution. In rat DRG neurons and F11-B9 cells, a fraction of the whole-cell Ba²⁺ current recorded in the presence of bicarbonate was resistant to block by saturating concentrations of Gd³⁺ (50–100 μM). The resistant current inactivated more rapidly than the original current giving the appearance that, under these conditions, Gd³⁺ block is more selective for the slowly inactivating component of the whole-cell current. Bicarbonate modification of Gd³⁺ block occurred both before and after ω-conotoxin block of N-type currents in rat DRG neurons, suggesting that even in the presence of bicarbonate, Gd³⁺ block was not selective for N-type currents.