| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J Neurophysiol (December 1, 2002). 10.1152/jn.00244.2002
Submitted on 4 April 2002
Accepted on 26 August 2002
Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland 21201
Vaillend, Cyrille,
Susanne E. Mason,
Matthew F. Cuttle, and
Bradley E. Alger.
Mechanisms of Neuronal Hyperexcitability Caused by Partial
Inhibition of Na+-K+-ATPases in the Rat CA1
Hippocampal Region. J. Neurophysiol. 88: 2963-2978, 2002. Extra- and intracellular records
were made from rat acute hippocampal slices to examine the effects of
partial inhibition of
Na+-K+-ATPases
(Na+-K+ pumps) on neuronal
hyperexcitability. Bath application of the low-affinity cardiac
glycoside, dihydroouabain (DHO), reversibly induced interictal-like
epileptiform bursting activity in the CA1 region. Burst-firing was
correlated with inhibition of the pumps, which was assayed by changes
in [K+]o uptake rates
measured with K+-ion-sensitive microelectrodes.
Large increases in resting
[K+]o did not occur. DHO
induced a transient depolarization (5-6 mV) followed by a long-lasting
hyperpolarization (~6 mV) in CA1 pyramidal neurons, which was
accompanied by a 30% decrease in resting input resistance. Block of an
electrogenic pump current could explain the depolarization but not the
hyperpolarization of the membrane. Increasing
[K+]o from 3 to 5.5 mM
minimized these transient shifts in passive membrane properties without
preventing DHO-induced hyperexcitability. DHO decreased synaptic
transmission, but increased the coupling between excitatory
postsynaptic potentials and spike firing (E-S coupling). Monosynaptic
inhibitory postsynaptic potential (IPSP) amplitudes declined to ~25%
of control at the peak of bursting activity; however, miniature
TTX-resistant inhibitory postsynaptic current amplitudes were
unaffected. DHO also reduced the initial slope of the intracellular
excitatory postsynaptic potential (EPSP) to ~40% of control. The
conductances of pharmacologically isolated IPSPs and EPSPs in
high-Ca/high-Mg-containing saline were also reduced by DHO by ~50%.
The extracellular fiber volley amplitude was reduced by 15-20%,
suggesting that the decrease in neurotransmission was partly due to a
reduction in presynaptic fiber excitability. DHO enhanced a late
depolarizing potential that was superimposed on the EPSP and could
obscure it. This potential was not blocked by antagonists of NMDA
receptors, and blockade of NMDA, mGlu, or GABAA
receptors did not affect burst firing. The late depolarizing component
enabled the pyramidal cells to reach spike threshold without changing
the actual voltage threshold for firing. We conclude that reduced
GABAergic potentials and enhanced E-S coupling are the primary
mechanisms underlying the hyperexcitability associated with impaired
Na+-K+ pump activity.
This article has been cited by other articles:
|
|
 |
|
  T. G. A. Money, C. I. Rodgers, S. M. K. McGregor, and R. M. Robertson Loss of Potassium Homeostasis Underlies Hyperthermic Conduction Failure in Control and Preconditioned Locusts J Neurophysiol, July 1, 2009; 102(1): 285 - 293. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. S. Richards, K. Bommert, G. Szabo, and R. Miles Differential expression of Na+/K+-ATPase {alpha}-subunits in mouse hippocampal interneurones and pyramidal cells J. Physiol., December 1, 2007; 585(2): 491 - 505. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Deng, V. Matagne, F. Banine, M. Frerking, P. Ohliger, S. Budden, J. Pevsner, G. A. Dissen, L. S. Sherman, and S. R. Ojeda FXYD1 is an MeCP2 target gene overexpressed in the brains of Rett syndrome patients and Mecp2-null mice Hum. Mol. Genet., March 15, 2007; 16(6): 640 - 650. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. E. Moseley, M. T. Williams, T. L. Schaefer, C. S. Bohanan, J. C. Neumann, M. M. Behbehani, C. V. Vorhees, and J. B Lingrel Deficiency in Na,K-ATPase {alpha} Isoform Genes Alters Spatial Learning, Motor Activity, and Anxiety in Mice J. Neurosci., January 17, 2007; 27(3): 616 - 626. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Kovacs, J. Kardos, U. Heinemann, and O. Kann Mitochondrial Calcium Ion and Membrane Potential Transients Follow the Pattern of Epileptiform Discharges in Hippocampal Slice Cultures J. Neurosci., April 27, 2005; 25(17): 4260 - 4269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Skov, S. Nedergaard, and M. Andreasen New Type of Synaptically Mediated Epileptiform Activity Independent of Known Glutamate and GABA Receptors J Neurophysiol, April 1, 2005; 93(4): 1845 - 1856. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. K. Kosmidis, O. Pierrefiche, and J.-F. Vibert Respiratory-Like Rhythmic Activity Can Be Produced by an Excitatory Network of Non-Pacemaker Neuron Models J Neurophysiol, August 1, 2004; 92(2): 686 - 699. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. G. Reich, S. E. Mason, and B. E. Alger Novel Form of LTD Induced by Transient, Partial Inhibition of the Na,K-Pump in Rat Hippocampal CA1 Cells J Neurophysiol, January 1, 2004; 91(1): 239 - 247. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N Rouach, M Segal, A Koulakoff, C Giaume, and E Avignone Carbenoxolone blockade of neuronal network activity in culture is not mediated by an action on gap junctions J. Physiol., December 15, 2003; 553(3): 729 - 745. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
