Cyclic nucleotides play critical roles in CNS functions. Many of their effects are mediated by protein kinases but an additional target may be represented by cyclic nucleotide-gated channels (CNGC).

We previously reported that CNGC activation causes membrane depolarization in medial vestibular nucleus neurons and increases their spontaneous firing rate. In the present study we focused on the possible role of CNGC in astrocytes.

By immunoblot and immunofluorescence experiments we found that cultured rat cortical astrocytes express the olfactory type A subunit (CNGA2). In voltage-clamp recordings, 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. 8-Br-cGMP elicited voltage-independent currents that were reduced by LCD and were unaffected by PKG blockade. A broad distribution of CNGA2 was also confirmed in astrocytes of the rat brain, and electrophysiological recordings from rat brain slices showed LCD-sensitive inward currents elicited by 8-Br-cGMP at -70 mV.

Since numerous physiological stimuli originating in neurons and astrocytes may raise the intracellular levels of cyclic nucleotides and activate astrocytic CNGC, these channels could be involved in the neuron-glia cross-talk and play a critical role in glia-mediated modulation of neuronal functions.