Gadolinium block of calcium channels: influence of bicarbonate.
The selectivity of block of voltage-activated barium (Ba2+) 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 omega-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 Ba2+ 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 microM). 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 omega-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.
Boland
L M
LM
Curriculum in Neurobiology, University of North Carolina, Chapel Hill 27599.
Brown
T A
TA
Dingledine
R
R
D000818:Animals; D001464:Barium / Q000494:pharmacology; D001639:Bicarbonates / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002460:Cell Line; D005682:Gadolinium / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D007700:Kinetics; D008674:Metals, Rare Earth / Q000494:pharmacology; D051379:Mice; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010525:Peripheral Nerves / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats
D001639:Bicarbonates; D002121:Calcium Channel Blockers; D008674:Metals, Rare Earth; D001464:Barium; D005682:Gadolinium