title: Loss of functional A-type potassium channels in the dendrites of CA1 pyramidal neurons from a mouse model of fragile X syndrome.
abstract: Despite the critical importance of voltage-gated ion channels in neurons, very little is known about their functional properties in Fragile X syndrome: the most common form of inherited cognitive impairment. Using three complementary approaches, we investigated the physiological role of A-type K(+) currents (I(KA)) in hippocampal CA1 pyramidal neurons from fmr1-/y mice. Direct measurement of I(KA) using cell-attached patch-clamp recordings revealed that there was significantly less I(KA) in the dendrites of CA1 neurons from fmr1-/y mice. Interestingly, the midpoint of activation for A-type K(+) channels was hyperpolarized for fmr1-/y neurons compared with wild-type, which might partially compensate for the lower current density. Because of the rapid time course for recovery from steady-state inactivation, the dendritic A-type K(+) current in CA1 neurons from both wild-type and fmr1-/y mice is likely mediated by K(V)4 containing channels. The net effect of the differences in I(KA) was that back-propagating action potentials had larger amplitudes producing greater calcium influx in the distal dendrites of fmr1-/y neurons. Furthermore, CA1 pyramidal neurons from fmr1-/y mice had a lower threshold for LTP induction. These data suggest that loss of I(KA) in hippocampal neurons may contribute to dendritic pathophysiology in Fragile X syndrome.
authors: Center for Learning and Memory, University of Texas at Austin, Austin, Texas 78712.
authors: Brandy N
authors: BN
authors: Routh
authors: Daniel
authors: D
authors: Johnston
authors: Darrin H
authors: DH
authors: Brager
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism / Q000502:physiology*; D003712:Dendrites / Q000378:metabolism / Q000502:physiology*; D004195:Disease Models, Animal; D005600:Fragile X Syndrome / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D017966:Pyramidal Cells / Q000378:metabolism / Q000502:physiology*
chemical_list: D015221:Potassium Channels