Possible modulatory role of voltage-activated Ca2+ currents determining the membrane properties of isolated pyramidal neurones of the rat dorsal cochlear nucleus

Voltage-activated Ca2+ currents have been studied in pyramidal cells isolat ed enzymatically from the dorsal cochlear nuclei of 6-11-day-old Wistar rat s, using whole-cell voltage-clamp. From hyperpolarized membrane potentials, the neurones exhibited a T-type Ca2+ current on depolarizations positive t o - 90 mV (the maximum occurred at about -40 mV). The magnitude of the T-cu rrent varied considerably from cell to cell (-56 to -852 pA) while its stea dy-state inactivation was consistent (E-50= -88.2 +/- 1.7 mV, s = - 6.0 +/- 0.4 mV). The maximum of high-voltage activated (HVA) Ca2+ currents was obs erved at about -15 mV. At a membrane potential of -10 mV the L-type Ca2+ ch annel blocker nifedipine (10 mu M) inhibited approximately 60% of the HVA c urrent, the N-type channel inhibitor omega-Conotoxin GVIA (2 mu M) reduced the current by 25% while the P/Q-type channel blocker omega-Agatoxin IVA (2 00 nM) blocked a further 10%. The presence of the N- and P/Q-type Ca2+ chan nels was confirmed by immunochemical methods. The metabotropic glutamate re ceptor agonist(+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (200 mu M) depressed the HVA current in every cell studied (a block of approximate ly 7% on an average). The GABA(B) receptor agonist baclofen (100 mu M) reve rsibly inhibited 25% of the HVA current. Simultaneous application of omega- Conotoxin GVIA and baclofen suggested that this inhibition could be attribu ted to the nearly complete blockade of the: N-type channels. Possible physi ological functions of the voltage-activated Ca2+ currents reported in this work are discussed. (C) 1999 Elsevier Science B.V. All rights reserved.