Voltage-gated Ca2+ conductances in acutely isolated guinea pig dorsal cochlear nucleus neurons

Although it is known that voltage-gated Ca2+ conductances (VGCCs) contribut e to the responses of dorsal cochlear nucleus (DCN) neurons, little is know n about the properties of VGCCs in the DCN. In this study, the whole cell v oltage-clamp technique was used to examine the pharmacology and voltage dep endence of VGCCs in unidentified DCN neurons acutely isolated from guinea p ig brain stem. The majority of cells responded to depolarization with susta ined inward currents that were enhanced when Ca2+ was replaced by Ba2+, wer e blocked partially by Ni2+ (100 mu M), and were blocked almost completely by Cd2+ (50 mu M). Experiments using nifedipine (10 mu M), omega Aga IVA (1 00 nM) and omega CTX GVIA (500 nM) demonstrated that a variety of VGCC subt ypes contributed to the Ba2+ current in most cells, including the L, N, and P/Q types and antagonist-insensitive R type. Although a large depolarizati on from rest was required to activate VGCCs in DCN neurons, VGCC activation was rapid at depolarized levels, having time constants <1 ms at 22 degrees C. No fast low-threshold inactivation was observed, and a slow high-thresh old inactivation was observed at voltages more positive than -20 mV, indica ting that Ba2+ currents were carried by high-voltage activated VGCCs. The V GCC subtypes contributing to the overall Ba2+ current had similar voltage-d ependent properties, with the exception of the antagonist-insensitive R-typ e component, which had a slower activation and a more pronounced inactivati on than the other components. These data suggest that a variety of VGCCs is present in DCN neurons, and these conductances generate a rapid Ca2+ influ x in response to depolarizing stimuli.