Aims: 

Cerebrocrast is a novel analog of dihydropyridines (DHP) synthesized in the Latvian Institute of Organic Synthesis. It was shown that cerebrocrast did not antagonize calcium influx in neuronal tissue and inhibited KCl – induced arterial contraction. It was hypothesized that cerebrocrast is a vascular – specific calcium antagonist. In our study we aimed to investigate direct effects of cerebrocrast on Ca_V1.2 L-type calcium channels in expression system.

Methods: 

In experiments we used HEK 293 cells transiently transfected with cDNAs encoding main subunit for smooth muscle isoform of Ca_V1.2 calcium channel together with b_2a and a₂d auxiliary subunits. 10 mM of Ca²⁺was used as a charge carrier.

Results: 

We measured effects of cerebrocrast on current through Ca_V1.2 calcium channel at holding potential (HP) of -80 mV and depolarized HP of -50 mV. Cerebrocrast inhibited calcium current in submicromolar concentrations in a concentration dependent manner at both holding potentials. Fitting data by Hill equation yielded IC₅₀ values of 585 ± 0.1 nM and 178 ± 0.1 nM and at HP -80 mV and -50 mV. Hill coefficient values were 0.63 ± 0.06 and 0.6 ±

0.2 at HP -80 mV and -50 mV. Cerebrocrast caused no significant changes of current voltage relationship of Ca_V1.2 calcium current at both tested holding potentials.

Conclusion: 

In conclusion, similar to traditional DHPs like nimodipine and nifedipine, cerebrocrast inhibited current through the Ca_V1.2 calcium channel in a voltage-dependent manner. However, its efficiency was more than one order of magnitude lower.

Supported by VEGA 2/7001 and APVV-51-027 404.