The Journal of Neurophysiology Vol. 81 No. 3 March 1999, pp. 985-998
Copyright ©1999 by the American Physiological Society

Voltage-Gated Ca²⁺ Conductances in Acutely Isolated Guinea Pig Dorsal Cochlear Nucleus Neurons

 ¹Department of Biomedical Engineering,  ²Department of Neuroscience, and  ³Department of OtolaryngologyHead and Neck Surgery, The Center for Hearing and Balance, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

Molitor, Scott C. and Paul B. Manis. Voltage-gated Ca²⁺ conductances in acutely isolated guinea pig dorsal cochlear nucleus neurons. 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 µM), and were blocked almost completely by Cd²⁺ (50 µM). Experiments using nifedipine (10 µM), Aga IVA (100 nM) and CTX 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°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.