Cyclic nucleotide-gated channels: new players in the regulation of neuronal and glial functions

Cyclic nucleotides play critical roles in a variety of CNS functions. Many of their effects are mediated by protein kinase activation, but we hypothesized that an additional target may be represented by cyclic nucleotide-gated channels (CNGC). We previously demonstrated expression of CNGC in medial vestibular nucleus neurons where their activation causes membrane depolarization leading to increase of spontaneous firing rate. In the present study we focused on possible role of CNGC in astrocytes. Immunoblot and immunofluorescence demonstrated expression of olfactory type A subunit (CNGA2) in cultured rat cortical astrocytes. In voltage-clamp, currents elicited in these cells by -100 to +100 mV ramps in the presence of the cGMP analogue, dB-cGMP, were reduced by the CNGC blockers, L-cis-diltiazem (LCD) and Cd2+. Reversal potentials of the LCD- and Cd2+ sensitive-currents were compatible with a mixed cation current. The cGMP analogue, 8-Br-cGMP elicited tonic currents at both positive and negative potentials, which were reduced by LCD and were not affected by PKG inhibitor. Astrocytic CNGA2 expression was confirmed in situ. In addition, 8-Br-cGMP elicited, at -70 mV, tonic inward currents in astrocytes from brain slices and its effects were inhibited by LCD. Since CNGC may be activated by several physiologically important agent released by neurons and astrocytes, our data suggest that these channels could be involved in the bidirectional communication between these cell types