Hyperexcitability of CA3 Pyramidal Cells in Mice Lacking the Potassium Channel Subunit Kv1.1

Valeri Lopantsev, Bruce L. Tempel, Philip A Schwartzkroin

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Purpose: To investigate further the membrane properties and postsynaptic potentials of the CA3 pyramidal cells in mice that display spontaneous seizures because of a targeted deletion of the Kcnal potassium channel gene (encoding the Kv1.1 protein subunit). Methods: Intracellular recordings were obtained from CA3 pyramidal cells in hippocampal slices prepared from Kcnal-null and control littermates. CA3 pyramidal cells were activated: orthodromically, by stimulating mossy fibers; antidromically, by activating Schaffer collaterals; and by injecting intracellular pulses of current. Responses evoked under these conditions were compared in both genotypes in normal extracellular medium (containing 3 mM potassium) and in medium containing 6 mM potassium. Results: Recordings from CA3 pyramidal cells in Kcnal-null and littermate control slices showed similar membrane and action-potential properties. However, in 33% of cells studied in Kcnal-null slices bathed in normal extracellular medium, orthodromic stimulation evoked synaptically driven bursts of action potentials that followed a short-latency excitatory postsynaptic potential (EPSP)-inhibitory PSP (IPSP) sequence. Such bursts were not seen in cells from control slices. The short-latency y-aminobutyric acid (GABA)A-mediated IPSP event appeared similar in null and control slices. When extracellular potassium was elevated and excitatory synaptic transmission was blocked, antidromic activation or short pulses of intracellular depolarizing current evoked voltage-dependent bursts of action potentials in the majority of cells recorded in Kcnal null slices, but only single spikes in control slices. Conclusions: Lack of Kv1.1 potassium channel subunits in CA3 pyramidal cells leads to synaptic hyperexcitability, as reflected in the propensity of these cells to generate multiple action potentials. The action-potential burst did not appear to result from loss of GABAA receptor-mediated inhibition. This property of CA3 neurons, seen particularly when tissue conditions become abnormal (e.g., elevated extracellular potassium), helps to explain the high seizure susceptibility of Kcnal-null mice.

Original languageEnglish (US)
Pages (from-to)1506-1512
Number of pages7
JournalEpilepsia
Volume44
Issue number12
DOIs
StatePublished - Dec 2003

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Kv1.1 Potassium Channel
Pyramidal Cells
Action Potentials
Potassium
Membrane Potentials
Seizures
Aminobutyrates
Synaptic Potentials
Excitatory Postsynaptic Potentials
Potassium Channels
Protein Subunits
GABA-A Receptors
Synaptic Transmission
gamma-Aminobutyric Acid
Hippocampus
Genotype
Neurons
Genes

Keywords

  • Burst discharge
  • CA3 pyramidal cells
  • Hippocampal slice
  • Hyperexcitability
  • Kcnal mutant mice
  • Kv1.1

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Hyperexcitability of CA3 Pyramidal Cells in Mice Lacking the Potassium Channel Subunit Kv1.1. / Lopantsev, Valeri; Tempel, Bruce L.; Schwartzkroin, Philip A.

In: Epilepsia, Vol. 44, No. 12, 12.2003, p. 1506-1512.

Research output: Contribution to journalArticle

Lopantsev, Valeri ; Tempel, Bruce L. ; Schwartzkroin, Philip A. / Hyperexcitability of CA3 Pyramidal Cells in Mice Lacking the Potassium Channel Subunit Kv1.1. In: Epilepsia. 2003 ; Vol. 44, No. 12. pp. 1506-1512.
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abstract = "Purpose: To investigate further the membrane properties and postsynaptic potentials of the CA3 pyramidal cells in mice that display spontaneous seizures because of a targeted deletion of the Kcnal potassium channel gene (encoding the Kv1.1 protein subunit). Methods: Intracellular recordings were obtained from CA3 pyramidal cells in hippocampal slices prepared from Kcnal-null and control littermates. CA3 pyramidal cells were activated: orthodromically, by stimulating mossy fibers; antidromically, by activating Schaffer collaterals; and by injecting intracellular pulses of current. Responses evoked under these conditions were compared in both genotypes in normal extracellular medium (containing 3 mM potassium) and in medium containing 6 mM potassium. Results: Recordings from CA3 pyramidal cells in Kcnal-null and littermate control slices showed similar membrane and action-potential properties. However, in 33{\%} of cells studied in Kcnal-null slices bathed in normal extracellular medium, orthodromic stimulation evoked synaptically driven bursts of action potentials that followed a short-latency excitatory postsynaptic potential (EPSP)-inhibitory PSP (IPSP) sequence. Such bursts were not seen in cells from control slices. The short-latency y-aminobutyric acid (GABA)A-mediated IPSP event appeared similar in null and control slices. When extracellular potassium was elevated and excitatory synaptic transmission was blocked, antidromic activation or short pulses of intracellular depolarizing current evoked voltage-dependent bursts of action potentials in the majority of cells recorded in Kcnal null slices, but only single spikes in control slices. Conclusions: Lack of Kv1.1 potassium channel subunits in CA3 pyramidal cells leads to synaptic hyperexcitability, as reflected in the propensity of these cells to generate multiple action potentials. The action-potential burst did not appear to result from loss of GABAA receptor-mediated inhibition. This property of CA3 neurons, seen particularly when tissue conditions become abnormal (e.g., elevated extracellular potassium), helps to explain the high seizure susceptibility of Kcnal-null mice.",
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N2 - Purpose: To investigate further the membrane properties and postsynaptic potentials of the CA3 pyramidal cells in mice that display spontaneous seizures because of a targeted deletion of the Kcnal potassium channel gene (encoding the Kv1.1 protein subunit). Methods: Intracellular recordings were obtained from CA3 pyramidal cells in hippocampal slices prepared from Kcnal-null and control littermates. CA3 pyramidal cells were activated: orthodromically, by stimulating mossy fibers; antidromically, by activating Schaffer collaterals; and by injecting intracellular pulses of current. Responses evoked under these conditions were compared in both genotypes in normal extracellular medium (containing 3 mM potassium) and in medium containing 6 mM potassium. Results: Recordings from CA3 pyramidal cells in Kcnal-null and littermate control slices showed similar membrane and action-potential properties. However, in 33% of cells studied in Kcnal-null slices bathed in normal extracellular medium, orthodromic stimulation evoked synaptically driven bursts of action potentials that followed a short-latency excitatory postsynaptic potential (EPSP)-inhibitory PSP (IPSP) sequence. Such bursts were not seen in cells from control slices. The short-latency y-aminobutyric acid (GABA)A-mediated IPSP event appeared similar in null and control slices. When extracellular potassium was elevated and excitatory synaptic transmission was blocked, antidromic activation or short pulses of intracellular depolarizing current evoked voltage-dependent bursts of action potentials in the majority of cells recorded in Kcnal null slices, but only single spikes in control slices. Conclusions: Lack of Kv1.1 potassium channel subunits in CA3 pyramidal cells leads to synaptic hyperexcitability, as reflected in the propensity of these cells to generate multiple action potentials. The action-potential burst did not appear to result from loss of GABAA receptor-mediated inhibition. This property of CA3 neurons, seen particularly when tissue conditions become abnormal (e.g., elevated extracellular potassium), helps to explain the high seizure susceptibility of Kcnal-null mice.

AB - Purpose: To investigate further the membrane properties and postsynaptic potentials of the CA3 pyramidal cells in mice that display spontaneous seizures because of a targeted deletion of the Kcnal potassium channel gene (encoding the Kv1.1 protein subunit). Methods: Intracellular recordings were obtained from CA3 pyramidal cells in hippocampal slices prepared from Kcnal-null and control littermates. CA3 pyramidal cells were activated: orthodromically, by stimulating mossy fibers; antidromically, by activating Schaffer collaterals; and by injecting intracellular pulses of current. Responses evoked under these conditions were compared in both genotypes in normal extracellular medium (containing 3 mM potassium) and in medium containing 6 mM potassium. Results: Recordings from CA3 pyramidal cells in Kcnal-null and littermate control slices showed similar membrane and action-potential properties. However, in 33% of cells studied in Kcnal-null slices bathed in normal extracellular medium, orthodromic stimulation evoked synaptically driven bursts of action potentials that followed a short-latency excitatory postsynaptic potential (EPSP)-inhibitory PSP (IPSP) sequence. Such bursts were not seen in cells from control slices. The short-latency y-aminobutyric acid (GABA)A-mediated IPSP event appeared similar in null and control slices. When extracellular potassium was elevated and excitatory synaptic transmission was blocked, antidromic activation or short pulses of intracellular depolarizing current evoked voltage-dependent bursts of action potentials in the majority of cells recorded in Kcnal null slices, but only single spikes in control slices. Conclusions: Lack of Kv1.1 potassium channel subunits in CA3 pyramidal cells leads to synaptic hyperexcitability, as reflected in the propensity of these cells to generate multiple action potentials. The action-potential burst did not appear to result from loss of GABAA receptor-mediated inhibition. This property of CA3 neurons, seen particularly when tissue conditions become abnormal (e.g., elevated extracellular potassium), helps to explain the high seizure susceptibility of Kcnal-null mice.

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KW - CA3 pyramidal cells

KW - Hippocampal slice

KW - Hyperexcitability

KW - Kcnal mutant mice

KW - Kv1.1

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