Effect of SR33805 on barium current and asymmetric intramembrane charge movement in freshly dissociated mouse cerebellar Purkinje neurons.
SR33805 is a novel calcium channel blocker that binds selectively and with high affinity to the alpha 1 subunit of the L-type calcium channel. The binding site for SR33805 is distinct from other classical calcium channel blockers although they interact allosterically. The block by SR33805 of the neuronal L-type calcium current has been reported [Romey, G. and Lazdunski, M., J. Pharmacol. Exp. Ther., 271 (1994) 1348-1352.]. In Purkinje neurons, the L-type calcium current is nearly absent. Nevertheless, we have shown the presence of intramembrane charge movement related to the dihydropyridines (DHP) receptor in these neurons. We show here that SR33805 has no effect on barium currents recorded in Purkinje cells but is a very potent blocker of intramembrane charge movement. It reduces charge movement to 48% of control with an IC50 of 0.5 nM.
Laboratoire de Neurobiologie Cellulaire et Moléculaire, CNRS, Gif-sur-Yvette, France. melliti@wat.nbcm.cnrs-gif.fr
K
K
Melliti
R
R
Bournaud
B
B
Bastide
J
J
Hidalgo
T
T
Shimahara
D000818:Animals; D001464:Barium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology*; D020746:Calcium Channels, L-Type; D002462:Cell Membrane / Q000502:physiology; D004553:Electric Conductivity; D007211:Indoles / Q000494:pharmacology*; D051379:Mice; D011689:Purkinje Cells / Q000502:physiology*; D013450:Sulfones / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D007211:Indoles; D013450:Sulfones; C084255:SR 33805; D001464:Barium