Aim: 

Cerebrocrast is a novel analog of a 1, 4-dihydropyridine (DHP). The aim of our study was to evaluate the effect of cerebrocrast on the Ca_V3.1 calcium channel.

Methods: 

We have used whole cell patch-clamp method. Ca_V3.1 calcium channel was permanently transfected into HEK 293 cells. Stock solution of cerebrocrast was prepared in DMSO in 10 mM concentration and was diluted into experimental concentration (10 nM, 100 nM, 1mM, 10 mM, 50 mM) prior to the experiment. The bath solution contained (mM): NaCl 135, HEPES 10, CaCl₂ 2, MgCl₂ 1, CsCl 5. The pipette consisted of (mM): CsCl 130, Na-ATP 5, TEA-Cl 10, HEPES 10, EGTA 10, MgCl₂ 5.

Results: 

Effect of cerebrocrast was evaluated at holding potentials of –100 mV and – 70 mV. Cerebrocrast inhibited current through the CaV3.1 calcium channel already in nanomolar concentrations. At both holding potentials 100 nM of cerebrocrast blocked 8% of the current amplitude. 50 mM of the drug inhibited 42% of the current amplitude measured at a holding potential of -100 mV. At a holding potential of –70 mV drug inhibited 49% of the current. Voltage-dependent enhancement of drug effectivity was not significant. 50 mM of cerebrocrast had no significant effect on the shape of the I-V curve and the position of their peaks.

Conclusion: 

In contrast to known DHPs such as nifedipine or isradipine, cerebrocrast was able to inhibit also the T-type Ca_V3.1 calcium channel.