The “Calcium Paradox” Discovery: Impact in Translational Research

An emerging word in biomedical research nowadays is the “translational research”. Basically, “translating” current knowledge from basic science to approaches for treating human disease - from bench to bedside - is the main concept. Our discovery entitled “calcium paradox” fits properly in this main concept. The enigma of the “calcium paradox” initiated with experiments performed in a classical study model of the neurotransmission (rodent vas deferens). Using this model, some studies performed since 1975 reported that reduction of Ca2+ entry by low concentrations of Ca2+ channel blockers (CCBs: verapamil, diltiazem or nifedipine) produced a paradoxical increase of the contractions mediated by sympathetic nerves, a phenomenon entitled as “calcium paradox”. Recent studies using adrenal chromaffin cells have also demonstrated that nifedipine caused a paradoxical increase of the catecholamine release. Because these compounds are blocking the L-type voltage-activated Ca2+ channels (VACCs), augmented nerve-mediated response due to increase of neurotransmitter release was an unexpected outcome. In 2013, we revealed that the Ca2+/cAMP signalling interaction (Ca2+/cAMP interaction) could properly explain the so-called “calcium paradox”. The original paper published by us in Cell Calcium (2013) has appeared four times in ScienceDirect TOP 25 Hottest Articles lists. In conclusion, these findings may dramatically impact in hypertension, neurological/psychiatric diseases, cancer and many other diseases, stimulating the development of new drugs for the pharmacotherapy of these diseases.