The dihydropyridine analogue cerebrocrast blocks both T-type and L-type calcium currents

Canadian Journal of Physiology and Pharmacology
Mária DrígelováLubica Lacinova

Abstract

Cerebrocrast is a novel lipophilic dihydropyridine derivative with potential neuroprotective and antidiabetic properties. We have analyzed its interaction with L-type (CaV1.2b) and T-type (CaV3.1) calcium channels using a whole-cell patch clamp in HEK 293 cells. Cerebrocrast inhibited current flux through both CaV1.2b and CaV3.1 channels. In both cases, the drug was about 10-fold less effective than neutral dihydropyridines, but more efficient than the charged dihydropyridine amlodipine. IC50 values for the CaV1.2b channel were 586 +/- 96 nmol/L and 178 +/- 78 nmol/L at holding potentials of -80 mV and -50 mV, respectively. Approximately 50 micromol/L of cerebrocrast was needed to block 50% of the current amplitude in the CaV3.1 channel, but this inhibition was not facilitated by shifting the holding potential from -100 mV to -70 mV. Cerebrocrast did not alter current kinetics in either investigated channel, and the inhibition of calcium current was partly reversible or irreversible. In conclusion, the interaction of cerebrocrast with CaV3.1 lacked the typical characteristics of a state-dependent interaction, and voltage-dependent inhibition of CaV1.2b was consistent with partial interaction with the inactivated state of the ch...Continue Reading

References

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Nov 1, 2008·The Journal of Pharmacology and Experimental Therapeutics·Edward Perez-ReyesIuliia Vitko
Nov 29, 2008·Cell Biochemistry and Function·Janina BriedeGunars Duburs

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