Possible modulatory role of voltage-activated Ca(2+) currents determining the membrane properties of isolated pyramidal neurones of the rat dorsal cochlear nucleus

• Published in: Brain research 1999-08, Vol.839 (1), p.109-119
• Main Authors: Harasztosi, C, Forsythe, I D, Szûcs, G, Stanfield, P R, Rusznák, Z
• Format: Article
• Language: English
• Subjects: Animals; Antibody Specificity; Baclofen - pharmacology; Calcium Channel Blockers - pharmacology; Calcium Channels - drug effects; Calcium Channels - physiology; Cochlear Nucleus - cytology; Cochlear Nucleus - physiology; Cycloleucine - analogs & derivatives; Cycloleucine - pharmacology; GABA Agonists - pharmacology; Immunochemistry; In Vitro Techniques; Membrane Potentials - physiology; Nifedipine - pharmacology; Patch-Clamp Techniques; Pyramidal Cells - physiology; Rats; Rats, Wistar; Receptors, Metabotropic Glutamate - agonists
• ISSN: 0006-8993
• DOI: 10.1016/S0006-8993(99)01723-0

Voltage-activated Ca(2+) currents have been studied in pyramidal cells isolated enzymatically from the dorsal cochlear nuclei of 6-11-day-old Wistar rats, using whole-cell voltage-clamp. From hyperpolarized membrane potentials, the neurones exhibited a T-type Ca(2+) current on depolarizations positive to -90 mV (the maximum occurred at about -40 mV). The magnitude of the T-current varied considerably from cell to cell (-56 to -852 pA) while its steady-state inactivation was consistent (E(50)=-88.2+/-1.7 mV, s=-6. 0+/-0.4 mV). The maximum of high-voltage activated (HVA) Ca(2+) currents was observed at about -15 mV. At a membrane potential of -10 mV the L-type Ca(2+) channel blocker nifedipine (10 microM) inhibited approximately 60% of the HVA current, the N-type channel inhibitor omega-Conotoxin GVIA (2 microM) reduced the current by 25% while the P/Q-type channel blocker omega-Agatoxin IVA (200 nM) blocked a further 10%. The presence of the N- and P/Q-type Ca(2+) channels was confirmed by immunochemical methods. The metabotropic glutamate receptor agonist (+/-)-1-aminocyclopentane-trans-1, 3-dicarboxylic acid (200 microM) depressed the HVA current in every cell studied (a block of approximately 7% on an average). The GABA(B) receptor agonist baclofen (100 microM) reversibly inhibited 25% of the HVA current. Simultaneous application of omega-Conotoxin GVIA and baclofen suggested that this inhibition could be attributed to the nearly complete blockade of the N-type channels. Possible physiological functions of the voltage-activated Ca(2+) currents reported in this work are discussed.