A Calcium Paradox in the Context of Neurotransmission

Abstract

The hypothesis of the calcium paradox has its origin in experiments done in neurogenically stimulated rat and mouse vas deferentia. Some old studies reported that reduction of Ca 2+ entry by mild concentrations of verapamil, diltiazem or nifedipine elicited the surprising augmentation of vas deferens contractions. Recent reports have also found that nifedipine caused a paradoxical augmentation of the exocytotic release of catecholamine elicited by paired depolarising pulses in voltage-clamped bovine chromaffin cells. Because these drugs are blocking the L-subtype of VACCs (voltage-activated calcium channels), augmented contraction and exocytosis was an unexpected outcome. Recent experiments in neurogenically-stimulated rat vas deferens have found a more drastic potentiation of contractions with the association of verapamil and cAMP-enhancer compounds. Thus, the interaction between the signalling pathways mediated by Ca 2+ and cAMP could explain those unexpected findings and the so-called calcium paradox.