title: Possible modulatory role of voltage-activated Ca(2+) currents determining the membrane properties of isolated pyramidal neurones of the rat dorsal cochlear nucleus.
abstract: 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.
authors.affiliation: Department of Physiology, University Medical School of Debrecen, H-4012, Debrecen, Hungary.
authors.forename: C
authors.initials: C
authors.lastname: Harasztosi
authors.forename: I D
authors.initials: ID
authors.lastname: Forsythe
authors.forename: G
authors.initials: G
authors.lastname: Szûcs
authors.forename: P R
authors.initials: PR
authors.lastname: Stanfield
authors.forename: Z
authors.initials: Z
authors.lastname: Rusznák
mesh_terms: D000818:Animals; D000918:Antibody Specificity; D001418:Baclofen / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D017626:Cochlear Nucleus / Q000166:cytology / Q000502:physiology*; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D007120:Immunochemistry; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018755:GABA Agonists; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D001418:Baclofen; D009543:Nifedipine