title: The whole-cell calcium current in acutely dissociated magnocellular cholinergic basal forebrain neurones of the rat.
abstract: 1. The electrophysiological and pharmacological characteristics of the calcium current (ICa) in acutely dissociated magnocellular cholinergic basal forebrain neurones from 11- to 14-day-old post-natal rats were studied using the whole-cell patch-clamp technique. 2. All cells exhibited a small transient low-voltage-activated (LVA) current with half-activation and half-inactivation potentials of -40.2 and -49.3 mV and slope factors for activation and inactivation of 4.82 and 3.85 mV per e-fold change in membrane potential (Vm) respectively. Activation and inactivation rates for the LVA current were highly voltage dependent. For test potential changes from -50 to -20 mV, the time-to-peak of the current decreased from 39.1 to 6.4 ms, and the time constant of current decay decreased from 81.7 to 15.5 ms. 3. A high-voltage-activated (HVA) component of ICa could be elicited at threshold voltages between -46 and -30 mV from a holding potential (VH) of -80 mV. The HVA current peaked around 0 mV; a 10-fold increase in [Ca2+]o produced a 13 mV positive shift in the peak, whilst the amplitude of the current showed an approximately hyperbolic relationship to [Ca2+]o with half-saturation at 2.5 mM. The transient phase of the HVA current could be described by two exponential functions with time constants tau fast and tau slow of 16.2 and 301 ms. Steady-state inactivation of the transient and extrapolated true sustained (pedestal) components of HVA current were described by Boltzmann equations, with half-inactivation potentials (slope factors) of -47.3 mV, (9.04) and -29.2 mV (11.8) respectively. 4. omega-Conotoxin (omega-CgTX; 100 nM) irreversibly inhibited a kinetically distinct component of HVA current but had no effect upon the transient LVA current. The omega-CgTX-sensitive current could not be distinguished from the control HVA current by the voltage dependence of its activation or inactivation rates. 5. Low concentrations of amiloride (< or = 300 microM) or Ni2+ (< or = 5 microM) selectively inhibited the transient LVA current, with IC50 values of 97 and 5 microM respectively. Cd2+ (< or = 1 microM) selectively blocked a component of HVA current. At higher concentrations, Cd2+ and Ni2+ were non-selective and totally blocked all components of ICa. 6. The lanthanide ions Gd3+ and La3+ produced saturable incomplete block of the HVA current. Maximally effective concentrations of Gd3+ (100 microM) or La3+ (30 microM) inhibited 76.5 and 41.2% respectively of the sustained component of HVA current with corresponding IC50 values of 2.2 and 1.1 microM.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Pharmacology, University College London.
authors.forename: T G
authors.initials: TG
authors.lastname: Allen
authors.forename: J A
authors.initials: JA
authors.lastname: Sim
authors.forename: D A
authors.initials: DA
authors.lastname: Brown
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000502:physiology*; D002478:Cells, Cultured; D002799:Cholinergic Fibers / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D020916:Conotoxins; D007477:Ions; D007700:Kinetics; D008564:Membrane Potentials / Q000502:physiology; D009532:Nickel / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D016548:Prosencephalon / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002121:Calcium Channel Blockers; D020916:Conotoxins; D007477:Ions; D010456:Peptides, Cyclic; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000584:Amiloride; D009532:Nickel; C055407:conotoxin GV; D000252:Calcium-Transporting ATPases; D009543:Nifedipine; D002118:Calcium