Modulatory effects of diadenosine polyphosphates on different types of calcium channels in the rat central neurons

Modulatory effects of diadenosine tetraphosphate (Ap4A) and diadenosine pentaphosphate (Ap5A) on Ca2+ channels were studied on isolated hippocampal neurons and synaptosomes taken from the rat midbrain. In experiments on synaptosomes obtained from the whole brain, Ap5A applied at a concentration of 100 mu M increased the intrasynaptosomal calcium level (measured by means of spectrofluorometry) for 26 +/- 1.8 nM, i.e., by 24 +/- 2%. Nifedipine failed to block this effect in synaptosomes and in hippocampal neurons. The high voltage-activated Ca2+ currents were identified by recording from freshly isolated CA3 neurons using a whole-cell patch-clamp technique. Current-voltage relationships were measured in control and after incubation with 5 mu M Ap5A In the majority of tested pyramidal neurons, the latter procedure resulted in a reversible increase in the high voltage-activated currents through Ca-2+ channels measured at a holding potential of -100 mV, but not of -40 mV. Potentiation of the currents through Ca2+ channels in hippocampal neurons as well as an increase in intrasynaptosomal [Ca2+] could be irreversibly blocked by 5 mu M omega-conotoxin, but not by 200 nM omega-Aga-IVA. These data indicate that diadenosine polyphosphates enhance the activity of N-type but not of L-type or P-type Ca2+ channels in many central neurons of the rat brain.