title: Potassium channels in hippocampal neurones are absent in a transgenic but not in a chemical model of Alzheimer's disease.
abstract: We have investigated using single channel patch-clamp methods potassium channel prevalence in hippocampal neurones from two animal models of AD. Experiments have been carried out on transgenic mice (Tg2576) carrying the Swedish mutation (K670N/M671L) and rats receiving ventricular infusions of okadaic acid. In cell-attached patches from hippocampal neurones from the Tg2576 and control littermate mice there were three principal unitary conductance - 22 pS, 111 pS and 178 pS. The two channels of intermediate and large conductance were voltage-dependent, highly active in cell-attached patches, activity decreasing markedly on hyperpolarisation. The large conductance channel was sensitive to TEA, iberiotoxin, was activated in excised inside-out patches by Ca 2+(i) and is the type I maxi-K+ channel. Significantly, there was a reduction in the prevalence of a TEA-sensitive 113 pS channel in neurones from TG2576 mice with a corresponding increase in prevalence of the maxi-K+ channel. There was no difference in the characteristics of maxi-K+ between patches in neurones from the transgenic and littermate controls. In the rat model single channel analysis was performed on hippocampal neurons from three groups of animals i.e. non-operated, and these receiving an infusion of vehicle or vehicle with okadaic acid. Three principal unitary conductances of around 18 pS, 118 pS and 185 pS were also observed in cell-attached recordings from these three groups. The intermediate and high conductance channels were blocked by TEA or 4-AP or 140 mM RbCl. There were no statistically significant differences in the channel prevalence or channel density between the control and test groups.
authors: Welsh School of Pharmacy, Cardiff University of Wales, Cardiff CF10 3NB, Wales, UK.
authors: B
authors: B
authors: Coles
authors: L A K
authors: LA
authors: Wilton
authors: M
authors: M
authors: Good
authors: P F
authors: PF
authors: Chapman
authors: K T
authors: KT
authors: Wann
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D009474:Neurons / Q000378:metabolism*; D019319:Okadaic Acid; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000145:classification / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D017207:Rats, Sprague-Dawley
chemical_list: D016564:Amyloid beta-Protein Precursor; D004791:Enzyme Inhibitors; D015221:Potassium Channels; D019319:Okadaic Acid