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

Abstract

Although it is known that voltage-gated Ca2+ conductances (VGCCs) contribute to the responses of dorsal cochlear nucleus (DCN) neurons, little is known about the properties of VGCCs in the DCN. In this study, the whole cell voltage-clamp technique was used to examine the pharmacology and voltage dependence of VGCCs in unidentified DCN neurons acutely isolated from guinea pig brain stem. The majority of cells responded to depolarization with sustained inward currents that were enhanced when Ca2+ was replaced by Ba2+, were blocked partially by Ni2+ (100 microM), and were blocked almost completely by Cd2+ (50 microM). Experiments using nifedipine (10 microM), omegaAga IVA (100 nM) and omegaCTX GVIA (500 nM) demonstrated that a variety of VGCC subtypes contributed to the Ba2+ current in most cells, including the L, N, and P/Q types and antagonist-insensitive R type. Although a large depolarization 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-threshold inactivation was observed at voltages more positive than -20 mV, indicating that Ba2+ currents were carried by high-voltage activated VGCCs. The VGCC subtypes contributing to the overall Ba2+ current had similar voltage-dependent properties, with the exception of the antagonist-insensitive R-type component, which had a slower activation and a more pronounced inactivation than the other components. These data suggest that a variety of VGCCs is present in DCN neurons, and these conductances generate a rapid Ca2+ influx in response to depolarizing stimuli.